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Propensity Analysis of Fitness

Levins (1968) has remarked that ''fitness enters population biology as a vague heuristic notion, rich in metaphor but poor in precision.'' No doubt this is accurate as a characterization of the unclarity surrounding the role of fitness in evolutionary theory, even among biologists who use the term. But such unclarity is quite compatible with the fact that fitness plays an essential explanatory role in evolutionary theory. It is to the task of increasing the precision of the concept of fitness as well as making explicit this explanatory role that we now turn. We have already seen that fitness is somehow connected with success at survival and reproduction, although it cannot be defined in terms of actual survival and reproductive success. Why have evolutionary biologists continued to confuse fitness with actual descendant contribution We believe that the confusion involves a misidentification of the post facto survival and reproductive success of an organism with the ability of an...

Fitness2 Fitness of Types

Having defined fitness1, we are in a position to define the fitness2 of types. As will become apparent in what follows, it is the fitness of types which figures primarily in explanations of microevolutionary change. Intuitively, the fitness of a type (genotype of phenotype) reflects the contribution of a particular gene or trait to the expected descendant contribution (i.e., the fitness1) of possessors of the gene or trait. Differences in the contributions of alternate genes or traits would be easy to detect in populations of individuals which were phenotypically identical except in regard to the trait or gene in question. In reality, though, individuals differ with regard to many traits, so that the contribution of one or another trait to fitnessj is not so straightforward. In fact, the notion of any simple, absolute contribution is quite meaningless. For a trait acts in conjunction with many other traits in influencing the survival and reproductive success of its possessors. Thus,...

Inclusive Fitness Theory

Within the individualistic tradition in biology, natural selection is widely thought to maximize a property called inclusive fitness, which is the sum of an individual's effects on the fitness of others multiplied by the probability that the others will share the genes causing the behavior. As Hamilton (1963 354-355) originally put it In this formulation, individuals evolve to maximize the fitness of ''their genes'' relative to other genes in the population, regardless of whether ''their genes'' are located in children, siblings, cousins, parents, and so on. Aid-giving toward relatives therefore ceases to appear altruistic, and becomes part of an individual's ''selfish'' strategy to maximize its inclusive fitness. Even sterility and death can be inclusive fitness maximizing if the positive effects on relatives are sufficiently great. Let us pursue this idea by considering an Aa female who mates with an aa male and produces a clutch of ten offspring, five of whom are Aa and the other...

Substance Misuse and Fitness for Interview

Withdrawal states can pose a bigger problem for the doctor assessing fitness for interview. Although most confessions made in these circumstances are reliable (74), it should be recognized that the person suffering from drug withdrawal may be particularly vulnerable to providing a false confession. Such persons may believe that compliance will result in early release and that the risks entailed in providing a false confession may seem worthwhile in the presence of an overwhelming desire to re-establish access to their supply of drugs (75). Although symptoms of mild withdrawal from opiates, for example, is considered unlikely to be a barrier to interview (62,73), the physical and mental distress occasioned by established withdrawal may seriously impair a suspect's fitness to undergo the somewhat threatening and difficult experience of police interrogation. When faced with a suspect suffering from severe withdrawal, the doctor should consider advising that the interview be deferred...

Exercise Fitness Training

The majority of FMS patients show poor strength, flexibility, and aerobic fitness. Research has noted the benefits of exercise, including decreased perception of pain and lowered pain threshold (141,142). The benefits of exercise for FMS patients, and in general, are based on reasonable scientific evidence (143,144). The question is whether exercise may also have negative consequences. FMS introduces postexer-tional pain into the situation, secondary to central sensitization. Because of the elements of FMS pathophysiology, exercise may be both good and bad for FMS patients, as they would experience more postexertional pain than non-FMS patients (145-147). This is important to note, as it may be this problem and not a patient's lack of adherence to a too rigorous exercise program that causes FMS patients to have not be able to endure long-term follow up with exercise programs.

Laws in the Evolutionary Process

My chapter ''Two Outbreaks of Lawlessness in Philosophy of Biology'' replies to Beatty's arguments and also to arguments for a similar conclusion advanced by Alexander Rosenberg in his 1994 book Instrumental Biology or the Disunity of Science. In reply to Beatty, I suggest that if a contingent evolutionary event E causes a biological generalization G to be true later on, then we should expect there to be a law linking E to G. This is consistent with Beatty's claim that if G is contingent on E (where E is contingent), then G is not a law. I also argue that the prevalence of relative significance controversies in evolutionary biology is no evidence for biology's lawlessness and that biology has not abandoned the principle of parsimony, when that principle is properly understood. Rosenberg's brief for lawlessness is based on the fact that biological properties are multiply realizable. Take a biological property like ''fitness'' or ''predator '' these predicates apply to organisms that...

Mills and John H Beatty

The concept of fitness is a notion of central importance to evolutionary theory. Yet the interpretation of this concept and its role in explanations of evolutionary phenomena have remained obscure. We provide a propensity interpretation of fitness, which we argue captures the intended reference of this term as it is used by evolutionary theorists. Using the propensity interpretation of fitness, we provide a Hempelian reconstruction of explanations of evolutionary phenomena, and we show why charges of circularity which have been levelled against explanations in evolutionary theory are mistaken. Finally, we provide a definition of natural selection which follows from the propensity interpretation of fitness, and which handles all the types of selection discussed by biologists, thus improving on extant definitions. whether it is worth bothering with them. But the fact is that there is a major problem in the foundations of evolutionary theory which remains unsolved, and which continues to...

The Charge of Circularity

According to the most frequently cited definitions of ''fitness,'' that term refers to the actual number of offspring left by an individual or type relative to the actual contribution of some reference individual or type. For instance, Waddington (1968, p. 19) sug gests that the fittest individuals are those which are ''most effective in leaving gametes to the next generation.'' According to Lerner (1958), ''the individuals who have more offspring are fitter in the Darwinian sense.'' Grant (1977, p. 66) construes fitness as ''a measure of reproductive success.'' And Crow and Kimura (1970, p. 5) regard fitness ''as a measure of both survival and reproduction'' (see also Dobzhansky 1970, pp. 101-102 Wilson 1975, p. 585 Mettler and Gregg 1969, p. 93). These definitions of ''fitness'' in terms of actual survival and reproductive success are straightforward and initially intuitively satisfying. However, such definitions lead to justifiable charges that certain explanations invoking fitness...

Socioecology and homology

A final criterion suggest that two behaviours are likely to be analogous if the biological role (or function) of those behaviours is similar, or if the two behaviours could have been subjected to similar selection pressures (e.g. Mayr, 1958). This definition is difficult to apply because it refers to selection in a broad way, stressing its significance but also highlighting the lack of available evidence concerning the nature of variation in behaviour, its genetic basis and its relation to fitness.

Propensity Analysis of Natural Selection

One consequence of our propensity interpretation of fitness is that the analysis also points to an improved definition of ''natural selection.'' As was noted earlier, the concepts of fitness and natural selection are inextricably bound so much so that misinterpretations of fitness are reflected in misinterpretations of natural selection. Thus, according to one of the more popular interpretations of natural selection, that process occurs whenever two or more individuals leave different numbers of offspring, or whenever two or more types leave different average numbers of offspring. For example, Crow and Kimura (1970) stipulate that ''selection occurs when one genotype leaves a different number of progeny than another'' (p. 173). Insofar as it is correct to say that the fittest are selected, this definition of ''selection'' clearly reflects a definition of ''fitness'' in terms of actual descendant contribution. In each of these cases, selection is construed as involving more than just...

The Long Term and the Short Term

The definition of fitness as expected number of offspring has a one-generation time scale. Why think of fitness in this way rather than as having a longer time horizon Consider figure 2.1 adapted from Beatty and Finsen (1989). Trait A produces more offspring than trait B (in expectation) before time t* however, after t*, A produces fewer offspring than B, and in fact A eventually produces zero offspring. The puzzle is that A seems to be fitter than B in the short term, whereas B seems to be fitter than A in the long term. Which of these descriptions is correct The issue of whether fitness should be defined as a short-term or a long-term quantity will be familiar to biologists from the work of Thoday (1953, 1958), who argued that fitness should be defined as the probability of leaving descendants in the very long run he suggests 108 years as an appropriate time scale. Thoday (1958, p. 317) says that a long-term measure is needed to obtain a definition of evolutionary progress. This...

When a One Generation Time Frame Is Inadequate

The concept of short-term fitness discussed so far has a one-generation time frame an organism at the egg stage has a probability p of reaching reproductive age and, once it is an adult, it has e as its expected number of offspring the product pe is its overall fitness. However, a one-generation time frame will not always be satisfactory for the concept of short-term fitness. Fisher's (1930) model of sex ratio shows why (Sober 1984). If, in expectation, one female has 5 sons and 5 daughters whereas another produces 10 daughters and 0 sons, how can their different sex-ratio strategies make a difference in their fitnesses Fisher saw that the answer is invisible if we think one generation ahead but falls into place if we consider two. The sex ratio exhibited by a female's progeny influences how many grandoffspring she will have. Other examples may be constructed of the same type. Parental care is a familiar biological phenomenon, but let us consider its extension care of grandoffspring....

Functional Role Of Neural Optimization

Finally, a larger question if one takes seriously the above instances of distinctively fine-grained neural optimization, a larger question emerges why is such extreme connectivity minimization occurring Of course, Save wire has obvious fitness value as explained earlier in reducing volume of a delicate metabolically costly tissue and in reducing signal propagation delays in a notably slow transmission medium. For instance, neuron volume minimization directly minimizes the significant metabolic pumping costs of maintaining ion concentrations across cell membranes (32). Nonetheless, such optimization nearly to absolute physical limits is only rarely encountered in biology (for instance, human visual and auditory system amplitude sensitivities under good conditions and the silk moth olfactory system, which can detect single molecules of mating pheromones 33-33b ). The usual view (e.g., 34 ) is that nature cannot afford to optimize, but instead, like any finite resource engineer, only...

Stochastic Variation in Offspring Number

Let us leave the question of short-term versus long-term behind and turn now to the question of whether fitness should be defined as a mathematical expectation. This is not an adequate definition when there is stochastic variation in viability or fertility. Dempster (1955), Haldane and Jayakar (1963), and Gillespie (1973, 1974, 1977) consider stochastic variation among generations Gillespie (1974, 1977) addresses the issue of within-generation variation. These cases turn out to have different mathematical consequences for how fitness should be defined. However, in both of them, selection favors traits that have lower variances. In what follows, I will not attempt to reproduce the arguments these authors give for drawing this conclusion. Rather, I will describe two simple examples that exhibit the relevant qualitative features. The trait with the lower variance can be expected to increase in frequency. The appropriate measure for fitness in this case is the geometric mean of offspring...

Cellular Senescence And Aging

However, it is consistent with the evolutionary hypothesis of antagonistic pleiotropy. This hypothesis predicts that the same traits that were selected to optimize fitness in young adult organisms can have unselected deleterious effects in aged organisms (170). The growth arrest associated with cellular senescence may be the selected trait, which suppresses tumorigenesis in young organisms. By contrast, the altered functions of senescent cells may be unselected traits that can have deleterious effects. Presumably, these deleterious effects are negligible in young tissues where senescent cells are rare. However, as organisms age, senescent cells accumulate (118-122). It is possible, then, that as senescent cells accumulate, their altered functions, particularly their secretory phenotype, compromise the physiology and integrity of tissues.

The Importance of Functional Assessment in Advanced Cancer and Cachexia

It goes without saying that the best way to treat cancer cachexia is to treat successfully the patient's cancer. For some patients oncological therapy may be influenced by chronological age 45,46 . However, it is often recognised that physiological age is perhaps more important. Functional assessment may provide one measure of this robustness and contribute to the shift in medical treatment delivery away from being unduly governed by chronological age and towards a greater use of markers of 'biological age' or risk. Understanding the relationship, therefore, between functional status and overall patient 'fitness' and 'reserve' is important.

Valid Individualism and Cheap Individualism

There is, however, another way to calculate fitness in the two-group model that leads to another definition of individual selection. Instead of separately considering evolution within groups and the differential fitness of groups, we can directly average the fitness of A- and S-types across all groups. Thus, the 2 A-types in groups one have 9.96 offspring and the 8 A-types in group two have 12.99 offspring, for an average fitness of 0.2(9.96) +0.8(12.99) 12.38. The 8 S-types in group one have 11.01 offspring and the 2 S-types in group two have 14.04 offspring, for an average fitness of 0.8(11.01) +0.2(14.04) 11.62. The average A-type individual is more fit then the average S-type individual, which is merely another way of saying that it evolves. Let us now return to the individualistic claim that ''virtually all adaptations evolve by individual selection.'' If by individual selection we mean the fitness of individuals averaged across all groups, we have said nothing at all. Since this...

The Evolution of Avirulence in Parasites and Diseases

In many interactions the exploiter cannot evolve to be avirulent it profits a fox nothing to spare the hare. But if the fitness of an individual parasite or its offspring is lowered by the death of its host, avirulence is advantageous. The myxoma virus, introduced into Australia to control European rabbits, at first caused immense mortality. But within a few years mortality levels were lower, both because the rabbits had evolved resistance and because the virus had evolved to be less lethal. . . . Because the virus is transmitted by mosquitoes that feed only on living rabbits, virulent virus genotypes are less likely to spread than benign genotypes italics mine . Avirulence evolves not to assure a stable future supply of hosts, but to benefit individual parasites. Thus, by the simple procedure of comparing the fitness of virulent and avirulent types across all hosts (see italicized portion of text), rather than within single hosts, the evolution of avirulence can be made to appear an...

Diploid Population Genetics and Evolutionary Game Theory

My final example involves a comparison between two seemingly different bodies of theory in evolutionary biology. Diploid population genetics models begin with a population of gametic types (A, a) which combine into pairs to form diploid genotypes (AA, Aa, aa). Selection usually is assumed to occur in the diploid stage, after which the genotypes dissociate back into gametes and the process is reiterated. The most common way for selection to occur in these models is for some genotypes to survive and reproduce better than others, the standard process of between-individual selection. In addition, however, it is possible for some alleles to survive and reproduce better than others within single individuals. For example, the rules of meiosis usually cause the two chromosome sets to be equally represented in the gametes. Some alleles manage to break the rules of meiosis, however, biasing their own transmission into the sperm and eggs of heterozygotes. The differential fitness of alleles...

Parallel Argument for the Human Sciences

As with any theory of human behavior, the first step is to specify the rules that cause people to choose among alternative behaviors, which serve as the analog of natural selection in an evolutionary model. Following Axelrod and others (Axelrod and Hamilton 1981 Brown et al. 1982 Pollock 1988), assume that humans adopt behaviors that maximize a given utility, relative to competing behaviors in the population. The utility might be pleasure (to a psychologist), annual income (to an economist), or genetic fitness (to a sociobiologist). The details of the utility are relatively unimportant because the hallmark of a hierarchical model is not the nature of the utility but the way it is partitioned into within- and between-group components. Consider, for example, a behavior that decreases the utility of self and increases the utility of others. If others include the entire population, then the utility of those expressing the behavior will be lower than those that do not, and the behavior...

The Optimization Criterion

Some assumption must then be made concerning what quantity is being maximized. The most satisfactory is the inclusive fitness (see the section Games between Relatives, below) in many contexts the individual fitness (expected number of offspring) is equally good. Often, as in the second and third of my examples, neither criterion is possible, and some other assumption is needed. Two points must be made. First, the assumption about what is maximized is an assumption about what selective forces have been responsible for the trait second, this assumption is part of the hypothesis being tested. Having considered the phenotype set and the optimization criterion, a word must be said about their relationship to Levins's (51) concept of a fitness set. Levins was explicitly concerned with defining fitness ''in such a way that interpopulation selection would be expected to change a species towards the optimum (maximum fitness) structure.'' This essentially group-selectionist approach led him to...

Quality of Life Measurement Health Related Quality of Life

The importance of quality of life may become especially prominent in palliative care of patients with malignant diseases, or with painful diseases of the musculoskeletal system, where mitigation of symptoms may be sought also in patients with cardiologic diseases, where treatment shall enhance physical fitness. Apart from being the primary goal of palliative measures, improved quality of life is also a byproduct of successful curative treatment. Consequently, the term quality of life (QoL) has been used very often in recent years. Many treatments have been advertised as being proven to enhance quality of life, while closer examination might reveal that, e.g. only the Karnofsky Index has been used to assess the single dimension of physical fitness by proxy rating, or that freedom of movement has been measured for a single extremity in angular degrees.

Games between Relatives

The central concept is that of ''inclusive fitness'' (33). In classical population genetics we ascribe to a genotype I a ''fitness'' W, corresponding to the expected number of offspring produced by I. If, averaged over environments and genetic backgrounds, the effect of substituting allele A for a is to increase W, allele A will increase in frequency. Following Oster et al. (74) but ignoring unequal sex ratios, Hamilton's proposal is that we should replace W by the inclusive fitness, Z , where where the summation is over all R relatives of I ri - is the fraction of J's genome that is identical by descent to alleles in I and Wj is the expected number of offspring of the jth relative of I. (If J I, then equation 6 refers to the component of inclusive fitness from an individual's own offspring.)

Chromatin Versus Other Determinants Of Aging

An intriguing example in this regard is the maternal-effect phenotype of mutations in the C. elegans CLK-1 gene (16). In Drosophila, an unexpected environmental input during development has been observed for flies selected for late-life fitness (13). In this case, the extended longevity characteristic of such flies is not evident unless the larvae are reared at a high density. Numerous examples of alternative life spans encoded by a single genome are cited by Finch (21), but remain at the phenomenological level. Of these, the most striking involves social insects such as honeybees, where alternative developmental pathways, queen versus worker, are associated with 10- to 100-fold differences in life span (21). Third, despite variation and plasticity, senescence can be described as having public versus private components (13). In this context, mechanisms involved in resistance to oxidative and other stresses may apply across multiple taxonomic groups. By contrast, age-related,...

Benefits and Precautions

Steinhoff BJ, Neususs K, Thegeder H, et al. Leisure time activity and physical fitness in patients with epilepsy. Epilepsia 1996 37(12) 1221-1227. 4. Jalava M, Sillanpaa M. Physical activity, health-related fitness, and health experience in adults with childhood-onset epilepsy a controlled study. Epilepsia 1997 38(4) 424-429.

Criticisms of the grandmother hypothesis

Current evidence suggests patrilocality as a conservative hominoid trait (Foley and Lee, 1989). Would grandmothering work as well in patrilocal groups as in the matrilocal groups it has been studied in The authors would rank grandmother's fitness benefit accruing from help to children of beneficiaries as greatest from help to daughter > sister > niece > son > nephew because of relatedness and paternity uncertainty. (Grandmother as mate guard is a role we have not examined. It might have interestingly different implications for life history.) For grandmothering to win over continued births, the only hopeful candidate would be help to daughter help to others is too heavily discounted. But help to any of these might be adequate to select for delayed senescence. Thus, the grandmother hypothesis could apply to either matrilocal or patrilocal settings. But grandmothers benefit most by living with their daughters and should favour matrilocality. Provisioning enables older juveniles...

Therapy Philosophy and Content

Second, return to developmentally appropriate activity is encouraged by increasing fitness and mobility, managing activity, rediscovering what was and can be valued in life, and developing methods of overcoming barriers to achieving valued activities. It is therefore important that the goals the young person has are ones that serve the person to do what he or she wants and is not imposed by others (parents, peers, or therapy staff). For example, walking 25 m may be a dull and pointless task to an adolescent, but walking to a caf with friends is an age-appropriate social and physical task that increases the possibility that the goal of walking 25 m is accomplished. Physical conditioning is also a core part of the program. However, physical exercise is undertaken in a number of settings to overcome the development of site-specific exercise behavior. Patients exercise in a room with no equipment, in their bedrooms, in a pool, and in a

Discussion and conclusions

This chapter concentrates on efforts to apply perspectives from life history theory in biology to data on contemporary hunters and gatherers. Topics include the allocation of resources between offspring number and fitness, age at first reproduction, lack of balance of fertility and mortality schedules, the special significance of helpers in human adaptation, and contrasting ideas about the evolution of post-reproductive life. These investigations share an interest in ecological contexts that may have shaped the life history parameters. Each attaches primary importance to rich resources that are difficult for juveniles to acquire (meat, deep roots

Brains Are Composed Primarily of Adaptive Problem Solving Devices

Adapted to the past The human brain, to the extent that it is organized to do anything functional at all, is organized to construct information, make decisions, and generate behavior that would have tended to promote inclusive fitness in the ancestral environments and behavioral contexts of Pleistocene hunter-gatherers and before. (The preagricultural world of hunter-gatherers is the appropriate ancestral context because natural selection operates far too slowly to have built complex information-processing adaptations to the post-hunter-gatherer world of the last few thousand years.)

Preventing False Confessions

The role of the forensic physician when assessing a suspect's fitness for interview is seen as fitting into this overall legal framework, the doctor's primary concern being to recognize any characteristics that might render the individual vulnerable to providing a false confession so that adequate safeguards can be put in place.

Definition of Fit for Interview

Until recently, there has been no clear definition of what precisely is meant by the term fit to be interviewed, and this has led to confusion among those doctors called on to perform these assessments (62). To address this deficiency, Norfolk (63) proposed a definition that was used as the starting point for discussion by a subgroup set up by the Home Office Working Party on Police Surgeons in the United Kingdom. That working party made an interim recommendation (64) that has now been modified and included in the 2003 revision of the Police and Criminal Evidence Act Codes of Practice (1), thus providing the first Parliamentary approved definition of the term fitness for interview. The Codes of Practice state that

The Natural Selection of HIV

The population of HIV is not stable during the asymptomatic period, however. HIV particles are constantly being reproduced because they continue to infect cells in the lymph nodes any time there is reproduction, mutation can occur. As a result, during the asymptomatic period new variants of HIV arise. Some of these HIV variants have mutated antigens. The change in antigens can be great enough that the antibodies that attacked the HIV particles produced early in the infection do not recognize the new variants. Thus, these new variants have higher fitness than the older variants as a result of their longer survival in the bloodstream. As the new HIV antigen variant becomes more common, the host's immune system develops an antibody to it, and HIV again begins to be cleared from the bloodstream until the next new antigen variant arises through mutation. In other words, the population of HIV inside the host is continually evolving, and the host's immune system is continually trying to...

Optimization Techniques

As indicated earlier, the computational intractability of exact methods for selecting the maximally diverse subset of compounds lead to the development of the DBCS and sphere exclusion approximate methods. An alternative approach is to use an optimization algorithm such as a genetic algorithm or simulated annealing. These algorithms can provide effective ways of sampling large search spaces and hence they are well suited to compound selection, provided that they are used with efficient methods of calculating diversity. For example, the Monte Carlo method has been combined with simulated annealing to select a diverse subset of compounds.170 An initial subset is chosen at random and its diversity is calculated. A new subset is then generated from the first by replacing some of the compounds with others chosen at random. If the new subset is more diverse than the previous subset it is accepted for use in the next iteration if it is less diverse, then the probability that it is accepted...

Higherlevel Generalization

Fitness is the supervenient biological property par excellens. What do a fit zebra, a fit dandelion, and a fit bacterium have in common Presumably, nothing much at the level of their physical properties. However, this has not prevented evolutionists from theorizing about fitness. I have already mentioned Fisher's theorem and there are lots of other lawful generalizations that describe the sources and consequences of fitness differences (Sober 1984). It might be objected that these generalizations are a priori, and so are not laws, properly speaking. This raises the question of whether laws must be empirical, but let us put that issue aside. If the multiple realiz-ability of a property makes it ''complicated,'' then fitness is complicated. And if the complexity of a property makes it impossible for us to discover qualitative, counterfac-tual supporting, and explanatory generalizations about the property, then we should have none available about fitness. But we do, as...

Protein Extraction Fractionation and Purification From Cyanobacteria

Analysis of the protein content of cells is a key complementary approach to genetic studies for understanding circadian regulation in cyanobacteria. In these organisms diurnal changes in protein levels of central clock components likely play a crucial role in generating rhythmicity (1) and, therefore, affect the fitness of the cell (2). The development of a variety of techniques for cyanobacterial protein fractionation and purification has provided us with knowledge of physical interactions among the Kai proteins and between KaiC and SasA (3,4), in vivo phosphorylation properties of KaiC (5), cycling of sigma factors (6), autophosphorylation activity of CikA (7), and intracellular dynamics of the Kai proteins during diurnal cycles (8).

Docking Programs GOLD

GOLD (genetic optimization for ligand docking) utilizes a genetic algorithm (GA),15,29 that mimics the process of evolution by applying genetic operators to a collection of putative poses for a single ligand (in GA terms, a population of chromosomes). GOLD chromosomes contain four genes. Two of these encode conformational information of the flexible parts of the protein and of the ligand, respectively. Each byte within these genes specifies a rotatable bond. The two remaining genes (feature arrays) encode hydrogen bonds and lipophilic interactions, respectively. Each potential hydrogen-bonding or lipophilic feature of the protein is represented by an array element. Each element either points to a corresponding partner on the ligand or contains an indication that the feature has no partner in the ligand. From the information contained in a chromosome, a 3D pose is generated (referred to as decoding) first a ligand conformation is generated by applying the bond rotations encoded in the...

Docking with Constraints

By introducing a bias during docking it is possible to influence the way poses are generated and which ones are preferentially kept. For example, in the DockIt program,106 one can apply distance constraints between ligand and protein atoms that are subsequently used during pose generation via a distance geometry approach. The GA of the GOLD program107-109 makes it easy to include different types of constraints in the fitness function, thus enabling the generation of biased poses. In the PhDock approach,110 as implemented in DOCK 4.0,111 one can perform pharmacophore-based docking by overlaying precomputed conformers of molecules based on to their largest 3D pharmacophore. The pharmacophore is then matched to predefined site points representing putative receptor interactions. Subsequently, all conformers are docked corresponding to the pharmacophore match and the fit of each individual conformer is scored. The advantage of this approach is twofold speed through a rapid pre-orientation...

Two Other Criticisms of the Multiple Realizability Argument

It might interest philosophers of mind who have these worries about multiply realized psychological properties to consider the multiply realized properties discussed in evolutionary biology. In cognitive science, it is difficult to point to many present-day models that are well-confirmed and that are articulated by describing multiply realizable properties this is mostly a hoped-for result of scientific advance. However, in evolutionary biology, such models are extremely common. Models of the evolution of altruism (Sober and Wilson 1998), for example, use the concept of fitness and it is quite clear that fitness is multiply realizable. These models have a useful generality that descriptions of the different physical bases of altruism and selfishness would not possess.

Clinical Significance Of The Cell Death Induced By Pr

Understanding the mechanisms behind these discordant responses to PI-based ART may provide important insight into T cell biology and the causes of CD4 cell loss during HIV infection. A variety of reasons behind discordant responses to ART has been proposed, including impaired replicative (and possibly pathogenic) fitness of a resistant virus direct cytotoxic effects of HIV protease viral escape, leading to autoimmunization and enhanced cytotoxic T cell function and possibly other unidentified mechanisms. An emerging body of literature indicates that a drug-resistant virus (especially a PI-resistant virus) has impaired replicative potential compared with a wild-type virus.43-49 Such studies use laboratory strains of HIV with point mutations in PR or clinical isolates containing PR mutations and compare replicative capacity between the mutant and wild-type virusus, either in simple replication assays or in competition experiments. More recently, these experiments have been performed in...

Intervention 2641 Physical Activity

Some studies of fatigue have included AYA. In a qualitative investigation of adolescents with cancer, clinical interventions identified as alleviating fatigue included maintenance of optimal fitness levels through an appropriate balance of rest and exercise, in addition to distraction and entertainment and relief from disease or treatment-related symptoms 4, 22 . A survey of cancer survivors who considered themselves athletes prior to diagnosis included young adults. Those who continued to exercise with modifications during treatment believed exercise made them less likely to develop health problems, and physical activity balanced with rest was an effective intervention for fatigue 23 . These studies have been complemented by the more rigorous research investigating the role of exercise in preventing and or alleviating cancer-related fatigue in adults. This has demonstrated that increased physical exercise is associated with less fatigue during and after treatment 3, 19 . These...

Protease Inhibitor Resistance

It now seems that at least three classes of mutations may result from subinhibitory HIV PI selective pressure primary HIV resistance mutations that impair viral replicative potential in vitro, secondary protease resistance mutations that may compensate for the impairment associated with primary mutations, and Gag-Pol cleavage site mutations. Examples include the primary resistance mutations D30N and L90M, both of which significantly impact viral replicative fitness compared with wild-type virus, whereas the secondary mutation, L63P, does not independently impact viral fitness.60 However, the addition of L63P to either of the primary mutations compensates for their impaired fitness significantly in the case of the L90M isolate and slightly for the D30N isolate.46 Alternately, defects within Gag-Pol processing may also impact replicative capacity, presumably by altering the efficacy of viral polyprotein processing, and virion packaging and progeny release. For example, paired pretherapy...

Associations Between Protease Mutations And Clinical Or Cd4 Outcome

The impact of protease mutations was studied extensively from the viral standpoint, but the effect of protease mutations upon the clinical course of disease received less attention. An emerging literature suggests that mutations in PR may be associated with a slower course of disease progression. Much of this literature is embedded in the literature concerning discordant response to therapy, in which the majority (if not all) of patients with immunologic discordance have viral isolates with PR resistance mutations, impaired viral fitness, and, therefore, impaired protease enzyme catalytic activity. Because there is strong evidence that HIV PR induces cell death through apopotosis or necrosis, we hypothesize that PR inhibitor-resistant mutations might attenuate or enhance HIV protease ability to induce cell death. Indeed, some data suggest that PR mutation may slow disease progression.49 Recently, the hypothesis that impaired PR catalytic activity will lead to enhanced CD4 T cell...

Autosomal Translocations and Compound Chromosomes

A phenomenon that characterizes both these types of rearrangement is that of negative heterosis, i.e., the hybrid is less fit than either parent. Inherent to this type of fitness relationship is the property of frequency-dependent selection whereby natural selection will drive one of the chromosomal types to fixation. The inference of this is that there must be an unstable equilibrium on either side of which selection will act to cause fixation of one chromosomal type or the other. If the fitness of both parental strains is 1, this unstable equilibrium will be when the frequencies of the two chromosomal types are equal. For other fitness levels the equilibrium point will change (Whitten 1971a,b). The presence of an unstable equilibrium means that if a gene is tightly linked to one of the chromsomal types it can be driven to fixation if the frequency of the particular chromosomal type is above the equilibrium frequency. It is in this way that these types of rearrangement were recruited...

Male Linked Translocations

Hybrid sterilty between different tsetse species was the first genetic principle to be proposed as a means of developing new ways to control insects (Potts 1944). The sterility generated when closely related species or geographically distinct populations are crossed can be genetic (Davidson 1969), cytoplasmic (Laven 1967a) or possibly a combination of the two. Genetic divergence between the members of species complexes can be of a degree that generates sterility in the hybrids and in general the heterogametic sex in the F1 generation tends to be the most affected (Haldane 1922, and see review Orr 1997). In most cases hybrid male sterility is accompanied by residual fertility in the F1 females as in most insect species the males are the heterogametic sex. However, in Lepidoptera the opposite is the case. The fact that F1 females remain partially fertile enables gene exchange to occur between sibling species in areas where the two cryptic species are sympatric. F1 hybrid males can show...

Scoring and Binding Energy Estimation

Scoring functions used in ligand design, as well as in ligand docking and virtual screening, are required to guide the sampling processes employed, as well as to estimate the fitness of the protein-ligand complex, usually in the form of a binding energy.93 As a consequence of the huge number of iterations conducted in each simulation, and often the processing of a large number of ligands, such scoring functions must be fast, which invariably means that accuracy is compromised, since several terms involved in the full thermodynamic cycle will be ignored. Nevertheless, scoring functions need to be robust in that they rank solutions highly with favorable steric and electrostatic interactions and rank ligands lower that are not complementary to a particular target, or are in an unfavorable configuration. The balance between hydrophobic interactions and hydrogen bonding, which represent the two main proponents of complex formation, is a key requirement for a successful scoring function...

Viral Factors That Influence Level Of Viremia

One potential factor that influences level of viremia is viral fitness. There are several examples of specific strains of HIV that are associated with less virulent infection. Early data for this were found in simian models. SIVmac239, a variant of simian immunodeficiency virus (SIV) with a premature stop signal in its Nef coding sequence, demonstrated the ability to replicate in cell culture, but disease was severely attenuated in infected rhesus monkeys.8 Similarly, a deletion in Nef causing attenuated disease was demonstrated in humans through accidental transmission of HIV via blood transfusion.

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Multiobjective Optimization

All the methods considered up to this point share a common element. They optimize a fitness function which comprises a set of weighted components. The effect is to turn the multiobjective problem into a single-objective optimization. There are a number of issues with this approach. The weights need to be defined empirically and may need to be varied from problem to problem. Whilst normalization of the properties may help this may in itself be nontrivial for certain properties. The very fact that weights are used will restrict the search space to particular regions. This is exemplified in Figure 10a which shows the results from multiple runs of the GA optimization algorithm SELECT with varying weights for the diversity and molecular weight components to the score. As a stochastic algorithm it is usual that a different result is obtained for multiple runs with the same settings and it could be argued that the algorithm has not been run for a sufficient number of iterations. On the other...

Ruth Mace And Clare Holden

Matrilineality has puzzled evolutionary anthropologists because it is not clear that male fitness is enhanced by passing resources on to a sister's son in preference to the man's own son. Tensions between men wishing to invest in their own children rather than in the mamtrilineal heirs are commonly reported. In the first descriptions of matrilineal societies by Western anthropologists (who were struck by the differences from their own culture), marriage and marital fidelity in matrilineal societies appeared relatively weak. If paternity uncertainty were very high, then fitness might be better enhanced by investing in your uterine sister's sons than in your wife's sons. But Hartung (1985) has demonstrated that paternity uncertainty would have to be at unrealistically high levels for this condition to hold. Hartung shows that matrilineality, whilst not adaptive for males, is adaptive for females under any level of paternity certainty below 1. This is because a grandmother's matrilineal...

Activity Guided Design

The methods and applications described up to this point have relied to a greater or lesser extent upon a computational model to guide the library design. An issue referred to above has been the vastness of chemical space the Ugi reaction can give rise to potentially millions of products, there are 64 million possible hexapeptides from the 20 naturally occurring amino acids. Are there alternative strategies for the discovery of active compounds in this vast space One such iterative approach to library design has been proposed and exemplified by several groups.310-312 The idea is simple in principle screen a subset of compounds from a library, measure the biological activity, input this information to an optimization algorithm, and generate the next set of compounds to synthesize and screen. This process is repeated until the desired activity level is reached or no improvement is seen. A GA has been the optimization method of choice. It relies upon a population of individuals, the...

Caloric Restriction And Aging

CR also draws a connection between reproduction and aging. In the absence of reproduction, suppressed either by adverse environmental conditions, or by ablation of germ cells in C. elegans or Drosophila, the life span in prolonged. This occurs presumably in an attempt to delay reproduction until a more favorable time in order to ensure the survival of the species. Thus, we begin to see stretching the life span as another potential mechanism of evolution, and successful aging as possibly subject to evolutionary pressure rather than being beyond its effects. It is obvious from an examination of the remarkable ranges of the life span among related species, that given certain appropriate ecological niches, species can indeed evolve new life history strategies, including decreases in rates of aging and substantial enhancements of longevities. Field studies of sibling species have provided strong support for this statement (36). The genomic remodeling that accompanies such enhanced life...

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Drink Drugs Driving Impairment Assessment Form

Note This form has been designed by Dr Ian F Wall on behalf of the Education and Research Committee of the Association of Police Surgeons for use by Police Surgeons (also known as Forensic Medical Examiners or Forensic Physicians) who have been trained in the use of Standardised Impairment Tests, The form is provided to assist Police Surgeons in determining whether a person has a condition, which may be due to drink or drugs and not necessarily due to impairment, It is to be regarded as an aide-memoire and it is therefore not necessary for all parts of the form to be completed. Some details are included so as to aid possible subsequent assessment of fitness for detention in custody. Where a test is abandoned the reasons should be recorded in Additional Particulars at 12, If the questions are read from a card, the wording should be identical to those used in this form and the card must remain available for production at court. On completion this form is the personal property of the...

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The docking poses found by GOLD are stored in MOL2 format. The ligand conformations are ranked according to their fitness score as calculated by the genetic algorithm. The final score is output in the mol2 file, and the best score for a particular ligand is transferred to a list (bestranking.lst). Results can be visualized using the usual software. A file called fit_pts.mol2 gives an impression of the size of the detected cavity.

Creactive protein

The degree of physical activity fitness can also affect CRP concentrations 82 . Individuals with a low cardiorespiratory fitness (who are also often sedentary) exhibit increased CRP levels compared with fit individuals. Such a difference remained significant even after adjustment for the degree of adiposity, assessed by the body mass index (BMI) 83 . Since endurance exercise training affects risk factors for coronary heart disease (glucose tolerance and insulin effectiveness, body composition, plasma lipoprotein levels, fibrinolysis and thrombosis, endothelial function, etc.) 84 , it is of interest to evaluate the extent to which exercise training might affect inflammation and, if so, what are the parameters affected by exercise training possibly associated with its beneficial effect on CRP levels.


A science may well progress even though its practitioners are unable to account for aspects of its foundations in any illuminating way. We believe that this has been the case with evolutionary theory, but that the propensity analysis of fitness which we have described captures the implicit content in biologists' usage of the term. The propensity interpretation allows us to reconstruct explanations of microevolutionary phenomena in such a way that these explanations appear to be entirely respectable and noncircular. By their form, and by inspection of the premises and conclusion, such explanations appear to satisfy Hempelian adequacy requirements for explanations, and even appear to incorporate recent modifications of the Hempelian model for inductive explanations (Coffa 1974). We chose an example of microevolutionary change, since we wanted the least complicated instance possible in order to illuminate the form of explanations utilizing fitness ascriptions. We know of no reason to...


Sedentary patients who are unmotivated to change their physical activity behaviour should then benefit from a brief consciousness-arousing session and be invited to read related information. Those who are motivated should benefit from a structured counselling session, receive written information, and a physical activity prescription using the existing structures within their environment (walking groups, fitness centres etc.).

Elliott Sober

The concept of fitness began its career in biology long before evolutionary theory was mathematized. Fitness was used to describe an organism's vigor, or the degree to which organisms ''fit'' into their environments. An organism's success in avoiding predators and in building a nest obviously contributes to its fitness and to the fitness of its offspring, but the peacock's gaudy tail seemed to be in an entirely different line of work. Fitness, as a term in ordinary language (as in ''physical fitness'') and in its original biological meaning, applied to the survival of an organism and its offspring, not to sheer reproductive output (Cronin 1991, Paul 1992). Darwin's separation of natural from sexual selection may sound odd from a modern perspective, but it made sense from this earlier point of view. Biologists came to see that this limit on the concept of fitness is theoretically unjustified. Fitness is relevant to evolution because of the process of natural selection. Selection has an...

Focus on Fit not

For most people, slowly working toward being fit rather than trying the latest fad diet is a more realistic and attainable way to achieve the positive health outcomes we all desire. In fact, fitness may be more important than body weight in terms of health. Studies show that fit but overweight people have better health outcomes than unfit slender people. In other words, lack of fitness has a higher risk associated with it than does excess body weight. Therefore, it makes more sense to focus on eating right and exercising than it does to focus on the number on a scale.


There is no reason for people with kidney failure to avoid strenuous activity. Patients can improve their exercise capacity considerably with regular workouts. Symptoms diminish and quality of life improves. When predialysis patients regularly exercised for four months, breathing capacity, muscular strength, and blood pressure all improved. There is no evidence, however, that exercise can defer dialysis current evidence indicates that progression is unaffected. The general health benefits of regular exercise have been widely publicized and include lowering blood pressure, lowering blood cholesterol level, and weight loss.


Entomogenous protozoa are an extremely diverse group with relationships ranging from commensal to pathogenic. They are generally slow acting and debilitating rather than quick and acute. Although they are undoubtedly important in natural biological regulation of insect populations, they do not possess the attributes necessary for a successful microbial insecticide. They can be extremely effective at reducing the fitness and fecundity of insects reared in culture so that they may have a very real negative effect on microbial insecticides (such as viruses) produced in vivo. Most protozoan infections cause sluggishness, irregular or slowed growth, resulting in reduced feeding, vigor, fecundity, and longevity (Lacey and Goettel 1995 Tanada and Kaya 1993).


Glare is another common presenting symptom. The patient complains that he or she cannot see so well in bright light and might even be wearing a pair of dark glasses. Glare is a photographic term but here it refers to a significant reduction in visual acuity when an extraneous light source is introduced. Light shining from the side is scattered in the catarac-tous lens and reduces the quality of the image on the retina. Glare becomes an important consideration when advising an elderly cataractous patient on fitness to drive. The visual acuity might be within the requirements laid down by law (seeing a number plate at 20.5 m) but only when the patient is tested in the absence of glare.

Future Trends

GA are a general optimization technique with good applicability in many fields, especially when the problem is so complex that it cannot be tackled with standard techniques. In chemometrics it has been applied especially in feature selection.10 GA try to simulate the evolution of a species according to the Darwinian theory. Each experimental condition (in this case, each model) is treated as an individual, whose performance (in the case of a feature selection for a calibration problem, it can be the explained variance) is treated as its fitness. Through operators simulating the fights among individuals (the best ones have a greatest probability of mating and thus

Genetic algorithms

A genetic algorithm performs its search by analogy to biological evolution.77 Possible solutions are represented as alleles in a chromosome, one chromosome per molecule. The genetic operators of mutation and crossover operate to optimize some fitness (scoring) function for the whole set of individuals.78 For example, in the GASP program each molecule is represented by one chromosome that contains alleles to describe each torsion angle and a second set of alleles that identify which atom is matched to a particular atom in a reference molecule. The fitness function of the genetic algorithm is a weighted combination of (1) the number and the similarity of the features that have been overlaid (2) the volume integral of the overlay and (3) the van der Waals energy of the molecular conformations defined by the torsion angles encoded in the chromosomes.79 Other programs use different chromosomes and fitness functions. All pharmacophore hypotheses are just that, hypotheses. For a scientist,...


Humans are expert at recruiting and distributing help. Hill and Hurtado suggest that many costs and benefits of alternative ways of behaving, growing and reproducing may be rendered unmeasurable by the ability of the individual who 'made an error' to cover it by recruiting help from kin, who also benefit from helping to remedy the miscalculation. Thus, a grandmother gains more fitness by going to go to help her daughter who bore too many children too fast (and thus risks being unable to feed them) than to her daughter who has few (depending on why the latter has few ). Grandmother's decision then reduces the effect of her daughter's 'miscalculation'. If instead the first daughter has more children because she


Reproductive senescence. In Reproduction in Mammals 4 Reproductive Fitness, ed. C.R. Austin and R.V. Short, pp. 210-33. Cambridge Cambridge University Press. Pennington, R. and Harpending, H.C., (1988). Fitness and fertility among Kalahari Kung. American Journal of Physical Anthropology 77, 303-19.

Figure 511

To test experimentally whether a trait is adaptive, we should exploit heritable variation to see if animals that have the trait in question are in fact more efficient foragers, and, ultimately, more efficient than those that do not. To this end, we need to show that the variance we find among colonies is heritable. To examine this question, we inbred queens from colonies of different populations with their brothers. The resulting F1 colonies were practically mirror images of their parental colonies (figure 5.12). For instance, if we cross Bombus terrestris terrestris from Germany with Bombus terrestris sassaricus from Sardinia, we obtain an F1 with intermediate red preference. This means there is a strong possibility of doing selection experiments in which we can test the influences of directional selection (Endler et al., 2001) and then perform fitness tests.

Water Gymnastics

A large number of exercise devices developed specifically for work in the water, such as swimming boards, balls, water noodles (made of highly buoyant soft plastic foam), dumbbells, and a large choice of equipment from the area of aqua-fitness guarantee a diversified exercise program. Relaxation techniques can also be done in the water, if the water temperature allows this. Exercises in which one partner lies on the back while being tugged or pushed through the water by the other partner are especially popular. The integration of music is obligatory in aqua-fitness training.


However, those patients with epilepsy without significant brain damage do, nonetheless, remain prone to cognitive impairment, particularly memory impairment, as a result of their epilepsy and its treatment. The potential impact of this cognitive impairment must be considered when assessing a patient with epilepsy's fitness for interview.


A detainee who is being adequately treated for myxedema poses no particular problem for the physician assessing fitness for interview. However, an individual with undiagnosed or undertreated hypothyroidism may exhibit mental manifestations that are as important as the physical. The typical picture is of mental lethargy, general dulling of the personality, and slowing of all cognitive functions. In particular, the patient with hypothyroidism shows deficits in memory, abstraction, conceptual organization, and mathematical ability (95).

Diabetes Mellitus

Although confusion is a prominent feature in patients who are slipping into hyperglycemic coma, this condition is rarely seen in police custody. Questions relating to fitness for interview and the potential reliability of a detainee's confession are more likely to involve those with hypoglycemia.


Rosenberg's brief for lawlessness rests on an entirely different set of arguments than Beatty's. Rosenberg (1994) uses the idea of supervenience to argue that, with one exception, there are no laws in biology. The one genuine law is what Rosenberg calls ''the theory of natural selection,'' by which he means Mary Williams' (1970) axiomati-zation. Rosenberg represents this axiomatization as saying that (i) there is an upper bound on the number of organisms in a generation, (ii) each organism has a fitness value, (iii) fitter traits increase in frequency and less fit traits decline, and (iv) populations show variation in fitness unless they are on the brink of extinction (p. 106). I want to raise two questions about this axiomatization. Proposition (iv) is probably true, but I do not see why the existence of variation in fitness should be regarded as a law. Statement (iii) is false if fitness means expected number of offspring and if fitness means actual number of offspring, it also is...

Natural Selection

If causing disease was its only effect, individuals who carry the allele would have lower fitness (that is, fewer surviving offspring) than individuals who do not carry the allele, because at least some of the carriers' offspring would have sickle-cell disease. Natural selection, the process described in Chapter 9 that results in an increase in the frequency of successful alleles and a decrease in unsuccessful ones, should cause the sickle-cell allele to become rare in a population. The reason that the sickle-cell allele is common in certain populations has to do with the advantage it provides to heterozygotes, individuals who carry one copy of the sickle-cell allele, in particular environments. tend to have narrower noses than populations in moist climates. Long, narrow noses appear to increase the fitness of individuals in dry environments, serving to increase the water content of inhaled air before it reaches the lungs. A narrower nose has a greater...


Crime statistics show a clear association between heavy drinking and criminal behavior, the association being most marked in relation to violent crimes. One review found that the incidence of alcohol-related violent crime ranged from 24 to 85 , which contrasted dramatically with the 12-38 incidence of alcohol-related nonviolent crime (118). Although some have confirmed the association between alcohol and crime (119,120), a direct causal link between the two has been disputed (121). Nonetheless, alcohol assumes an importance in clinical forensic medicine because of its link with criminal activity and by virtue of the significant role it plays in a large number of assessments regarding fitness for detention (122-124). Accordingly, a thorough understanding of the metabolism, effects, and problems associated with


Genetic methods (genetic algorithms and evolutionary programming) store multiple solutions. These solutions form a population of members. Each member has an associated score or fitness. During the search for the global optimal solution successive new populations are created by a procedure involving selection of the fittest members. These members then have offspring to create a new population. Differences arise in how the methods generate offspring. In a genetic algorithm two solutions are mated to form a new offspring solution. In evolutionary programming each member of the population generates an offspring by mutation.

Late Century Reform

On the whole, physical reformers in the last twenty or so years of the century could look back on a lot of specific achievements in the field of public hygiene, many of which had been (or were in the process of becoming) institutionalized. The key reform in Britain was obviously the capture of central and local government and the creation of an ethos of sanitary need. Municipal socialists and commercial developers were now starting to rebuild the towns through mass slum clearances, all new housing was fully plumbed and drained, and a whole cadre of doctors had moved into public health. A great deal of municipal and state effort was now also being put into adult physical fitness training, and in the new state and Church schools children were now being exercised and taught the basic rules of hygiene and popular physiology, collectively, for the first time. The Early Hours Movement released and in part was designed to release male and female clerks and shop assistants from their work in...

Field Trials

The field trials carried out using compound chromosome strains in L. cuprina remain the only field experience with pest insects using this system. For almost 7 months about 1 million larvae carrying compound chromosomes were released into a 10 sq. kilometer valley. Genetic analysis in the year of the releases revealed that males from the released strain were mating with the wild females and that females from the released strain were ovipositing in sheep. At the end of the release period, 90 of the field matings were between flies carrying compound chromosomes, and it was expected that the compound chromosome type would eliminate the normal chromosome. However, the next year no compound chromosome individuals could be found in the field, indicating that the fitness of the released strain was much inferior to that of the field strain (Foster et al. 1985b).


This problem is illustrated by a more recent study from Germany (73). Thirty-four methadone substitution patients, all of them volunteers, were subjected to a battery of psychological tests. Twenty-one of these patients had to be excluded from the study because the toxicological analysis of repeated blood and urine samples revealed the presence (or possibly chronic use) of substances other than methadone. Of the remaining 13 (age range 26 to 42 years, 8 males and 5 females) 6 were selected who, based on the impression of the physicians, could be described as optimal methadone patients. Although some personality scales and psychopathological findings revealed shortcomings for a few of these patients, they could not be regarded as factors ruling out driver fitness, and the authors concluded that under certain conditions, long-term methadone maintenance patients under strict medical supervision do not suffer significant driving impairment, providing that no other drugs have been taken.

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Genetic algorithms belong to the more general class of evolutionary algorithms that have become an important optimization methodology within computational chemistry.114 GAs are loosely connected with the principles of Darwinian evolution as shown in the general process flow in Figure 7 and much of the terminology is borrowed from this field.115 Thus, there is the concept of a population that evolves under the constraint of some user-defined objective function. The objective function is used to compute a score or fitness for each individual within the population that is used, in turn, to assess the likelihood of that individual generating offspring at the next generation. The fitter the individual the more likely it is to breed. Each individual is represented by a chromosome (genotype) that encodes the particular problem to be optimized in a series of genes. At each generation chromosomes can mutate (one individual generates one offspring) or can breed with another individual via a...

Clinical Examination

A series of divided attention tests should be performed including the Romberg test, finger-nose test, one-leg-stand test, and walk and turn test. A survey of forensic physicians' opinions within Strathclyde police demonstrated concerns regarding the introduction of standardized field sobriety tests with the walk and turn test and the one-leg-stand test, causing the highest levels of concern (90). The mental state should be assessed and consideration given to obtaining a sample of handwriting. Fitness for detention is of paramount importance, and any person who is not fit to be detained because of illness or injury should be transferred to hospital and not subjected to a Section 4 assessment. If the person refuses to consent to an examination, it is prudent to make observations on his or her manner, possible unsteadiness, etc. and make written note of these.

CMV dynamics

By the use of serial measurement of the appearance of CMV viraemia post-transplant, and then following the trajectory of the quantity time curve, it was possible to show that the doubling time was approximately 2 days in bone marrow transplant patients (n 18). The half-life of decline from a high viral load following treatment with intravenous ganciclovir was shown to be 2.5 days in AIDS patients (n 35), 1.5 days in bone marrow transplant patients (n 11) and 2.4 days in liver transplant patients (n 12). These differences were not attributable to differences between the groups of patients but were a manifestation of the timing of sample collection. Specifically, when samples were obtained on alternate days from AIDS patients, it was possible to reduce these upper limit estimates of the halflife down to approximately 1 day, whether measured in blood or in urine 14 . Finally, in patients where resistant strains were evolving under the selective pressure of ganciclovir, it was possible to...


To certify or to participate in the certification of the fitness of prisoners or detainees for any form of treatment or punishment that may adversely affect their physical or mental health and which is not in accordance with the relevant international instruments or to participate in any way in the infliction of any such treatment or punishment that is not in accordance with the relevant international instruments.

Age at first birth

Like Stearns and Koella (1986), Hill and Hurtado sought the strategy that maximised fitness, measured as r (intrinsic rate of increase). Stearns (1992 p. 148) points out that Kozlowski and Wiegert (1987) examined maximisation of lxmx and obtained the prediction that faster growth predicted later maturity. This point, apparently commonplace to life history theorists, is noted as a warning to us 'end-users' that the field is complex, in flux, and there is as yet no single 'right' model. They link these observations of developing hunting success to the idea that humans mature late because this allows them more time to acquire fitness-enhancing skills (Lancaster and Lancaster, 1983 Bogin, 1990 Lancaster, 1997). Kaplan's interest in human capital theory (1994), often used to discuss the costs and benefits of staying on at school, may lead to a more explicit version of this view. These authors have argued in another direction (Blurton Jones, Hawkes and O'Connell, 1997 Hawkes, O'Connell and...

Clinical Studies

Pain relievers present in the brain), may inhibit seizures the effect may also be indirect. Some investigators speculate that daily aerobic exercise acts as a stress vaccine whereby catecholamines (including adrenaline) released in the body during stressful events seem to decrease as physical fitness increases (14). One well-controlled study in patients with congestive heart failure revealed significant improvements in stress management for patients entered into an exercise program (2). If stress is a significant provocative factor in causing seizures, then exercise may indirectly reduce seizure frequency.

Fitness Fundamentals

Fitness Fundamentals

Everyone knows that good health is something to be treasured and respected, but few make a conscious habit to pay attention to their health until the red flag appears which in most cases signifies really poor health conditions. Get fit with the info here.

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