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Adaptation and the cost of complexity.

Adaptation is characterized by the movement of a population toward a many-character optimum, movement that results in an increase in fitness. Here I calculate the rate at which fitness increases during adaptation and describe the curve giving fitness versus time as a population approaches an optimum in Fisher's model of adaptation. The results identify several factors affecting the speed of adaptation. One of the most important is organismal complexity--complex organisms adapt more slowly than simple ones when using mutations of the same phenotypic size. Thus, as Fisher foresaw, organisms pay a kind of cost of complexity. However, the magnitude of this cost is considerably larger than Fisher's analysis suggested. Indeed the rate of adaptation declines at least as fast as n-1, where n is the number of independent characters or dimensions comprising an organism. The present results also suggest that one can define an effective number of dimensions characterizing an adapting species.

Adaptation, Physiological↗

Segment-based dose optimization using a genetic algorithm.

Intensity modulated radiation therapy (IMRT) inverse planning is conventionally done in two steps. Firstly, the intensity maps of the treatment beams are optimized using a dose optimization algorithm. Each of them is then decomposed into a number of segments using a leaf-sequencing algorithm for delivery. An alternative approach is to pre-assign a fixed number of field apertures and optimize directly the shapes and weights of the apertures. While the latter approach has the advantage of eliminating the leaf-sequencing step, the optimization of aperture shapes is less straightforward than that of beamlet-based optimization because of the complex dependence of the dose on the field shapes, and their weights. In this work we report a genetic algorithm for segment-based optimization. Different from a gradient iterative approach or simulated annealing, the algorithm finds the optimum solution from a population of candidate plans. In this technique, each solution is encoded using three chromosomes: one for the position of the left-bank leaves of each segment, the second for the position of the right-bank and the third for the weights of the segments defined by the first two chromosomes. The convergence towards the optimum is realized by crossover and mutation operators that ensure proper exchange of information between the three chromosomes of all the solutions in the population. The algorithm is applied to a phantom and a prostate case and the results are compared with those obtained using beamlet-based optimization. The main conclusion drawn from this study is that the genetic optimization of segment shapes and weights can produce highly conformal dose distribution. In addition, our study also confirms previous findings that fewer segments are generally needed to generate plans that are comparable with the plans obtained using beamlet-based optimization. Thus the technique may have useful applications in facilitating IMRT treatment planning.

Algorithms↗

The orthopaedic workforce in Queensland now and into the twenty-first century.

The objectives of this study were to determine the number and distribution of orthopaedic surgeons in Queensland at present and to assess the adequacy of trainee intake for the future. Characteristics of the orthopaedic workforce in Queensland in 1990 were analysed with regard to the total number of orthopaedic surgeons, their regional distribution, their ratio to the population and their age distribution. Similar statistics were derived for the years 1981 and 1986 and trends were examined. By projecting these trends, the number of surgeons likely to be practising in 2001 was estimated. Using projected population figures, the number of orthopaedic surgeons required in 2001 was calculated, assuming an optimum ratio of surgeons to population of one per 25,000. It was found that in 1990 sufficient orthopaedic surgeons were practising in Queensland but that there was some maldistribution. With the increased intake of five new training registrars per year, the number of orthopaedic surgeons in Queensland in 2001 should be appropriate, as long as current trends continue.

Forecasting↗

A model for peak and width of signaling windows: Ips duplicatus and Chilo partellus pheromone component proportions--does response have a wider window than production?

Pheromone communication systems have a reliable signal with a restricted window of amounts and ratios released and perceived. We propose a model based on a Gaussian response profile that allows a quantification of the response peak (location of optimum) and a measure of the peak width (response window). Interpreting the Gaussian curve, fitted by nonlinear regression (NLR), as a standard normal distribution, the peak location equals the mean (it) and the window width equals 2 x the standard deviation (2sigma). The NLR procedure can provide an objective measure for both peak location and width for a wide range of data sets. Four empirical data sets as well as 10 literature data sets were analyzed. The double-spined spruce engraver, Ips duplicatus, was field tested in four populations to find the optimum proportion for attraction to the two male aggregation pheromone components, ipsdienol (Id) and (E)-myrcenol(EM), ranging from 0 to 100% of Id. Tests in Norway and the Czech Republic confirmed the preference of western populations for a blend between 50 and 90% Id. A population in Inner Mongolia showed a preference for traps with the 10 and 50% Id baits. The NLR fitted values for response peak and width (mu; 2sigma) were: Norway 0.64, 0.73; Czech Republic 0.53, 0.73; NE China 0.77, 0.29; and Inner Mongolia 0.33, 0.50. The signal produced by Norwegian field-collected males had a narrower window width (2sigma = 0.12). Males of the maize stem borer, Chilo partellus, were tested in a flight tunnel for their response to variation in the two major female sex pheromone gland components, (Z)- l1-hexadecenal and the corresponding alcohol (OH). Variation of the alcohol in seven levels from 2 to 29% OH showed the highest male response for 17% OH. For all behavioral steps, the peak of male response was near mu = 0.14, while the window width fell from 2sigma = 0.5 to 0.2 for eight sequential behavioral steps from take-off to copulation. Female production had a similar peak location (mu = 0.13) but a narrower width, 2sigma = 0.14. Literature data from other moth species showed similar patterns, with a wider male response relative to the female production windows. Literature data on response to enantiomer ratios in a hymenopteran and to pheromone amounts in a dipteran were also described by our model. In a bark beetle population (Ips pini), with two hybridizing enantiomeric strains, the production peaks were narrower (0.1) than the response peaks (0.5). Thus, it in general, seems that in the pheromone systems analyzed, the width of the response window (2sigma = 0.1 to 0.8) is larger than that of the production window (2sigma = 0.03 to 0.14), irrespective of the sex of the sender.

Animals↗

Effects of pre-conditioning and microbial composition on the sensing efficacy of a BOD biosensor.

Sensitivity and the linear range of BOD measurement of a microbial BOD sensor using a mixed cell population of Bacillus subtilis and Bacillus licheniformis 7B depend significantly on the proportion of the two microorganisms and on the cell population immobilized on the biofilm. Optimum characteristics were obtained with equal proportion of the two microorganisms and an immobilized cell population of not less than 10(8) in the biofilm. Pre-conditioning of newly installed biofilm was best carried out in high BOD solutions and the time required to fully activate the microbial system decreased with increasing cell population. Fully activated biofilm remained stable and gave reproducible results for over 200 measurements covering a time period of more than 2 months. The technique of cell immobilization used in the present study provided a close control of the population and composition of the two microorganisms in the biofilm. Consistent and reproducible quality biofilms can therefore be produced for the preparation of the microbial BOD sensor.

Bacillus↗

Evolution and path models in human behavioral genetics.

The evolutionary implications of the path-analysis model most often used in human behavior genetics are examined. With directional selection, a model of pure vertical environmental transmission does not respond in a fully adaptive fashion. Unless the coefficients of transmission are exactly 0.50, the population mean will not equilibrate at the selective optimum over time. If there is both genetic and vertical environmental transmission, then the population mean can equilibrate at the selective optimum. In the presence of genetic transmission, vertical environmental transmission increases population fitness and has a strong effect on the rapid movement of the mean toward the selective optimum. This raises the intriguing paradox of why empirical evidence suggests that vertical environmental transmission is usually small when it possesses such important fitness properties.

Biological Evolution↗

[Monitoring of vancomycin plasma levels in patients undergoing hemodialysis].

OBJECTIVE: The aim of this study was to confirm whether patients undergoing dialysis and treated with vancomycin 1 g/week or 500 mg/48 hours reach optimum plasma levels (10-25 mcg/ml). METHOD: Thirty two patients were included with a total number of 34 infectious events. The most commonly used dose was 1 g/week (67.6% of infectious events), versus 500 mg/48 hours (32.4%). Low ultrafiltration membranes were used more frequently (64.7%) than high ultrafiltration membranes (35.3%).Vancomycin was infused over an one-hour period during the last hour of the hemodialysis session and plasma samples were drawn prior to the beginning of the session. Samples were analyzed using fluorescent polarization immunoassays. RESULTS: Mean concentration results for the total population did not reach optimum values (10-25 mg/ml). In the group receiving 500 mg/48 hours, optimum mean values were not reached in any of the determinations, whereas in the group receiving 1 g/week, optimum values were reached in the fourth determination. Mean plasma levels of the antibiotic were below optimum values, regardless the type of membrane used, either low or high ultrafiltration. CONCLUSIONS: Based on the above results, we recommend titration of the vancomycin dose in this group of patients and the administration of a loading dose of 20 mg/kg during the last hour of the hemodialysis session, followed by a maintenance dose of 7 mg/kg after each session, as well as the monitoring of the drug levels in this group of patients.

Aged↗

Maternal-zygotic gene conflict over sex determination: effects of inbreeding.

There is growing evidence that sex determination in a wide range of organisms is determined by interactions between maternal-effect genes and zygotically expressing genes. Maternal-effect genes typically produce products (e.g., mRNA or proteins) that are placed into the egg during oogenesis and therefore depend upon maternal genotype. Here it is shown that maternal-effect and zygotic genes are subject to conflicting selective pressures over sex determination in species with partial inbreeding or subdivided populations. The optimal sex ratios for maternal-effect genes and zygotically expressing genes are derived for two models: partial inbreeding (sibmating) and subdivided populations with local mating in temporary demes (local mate competition). In both cases, maternal-effect genes are selected to bias sex determination more toward females than are zygotically expressed genes. By investigating the invasion criteria for zygotic genes in a population producing the maternal optimum (and vice versa), it is shown that genetic conflict occurs between these genes. Even relatively low levels of inbreeding or subdivision can result in maternal-zygotic gene conflict over sex determination. The generality of maternal-zygotic gene conflict to sex determination evolution is discussed; such conflict should be considered in genetic studies of sex-determining mechanisms.

Alleles↗

Generation of mucosal cytotoxic T cells against soluble protein by tissue-specific environmental and costimulatory signals.

We compared peripheral and mucosal primary CD8 T cell responses to inflammatory and noninflammatory forms of antigen in a T cell-adoptive transfer system. Immunization with the soluble antigen, ovalbumin (ova), administered i.p. or orally without adjuvant, activated nonmucosal CD8 T cells but did not induce cytotoxic activity. However, after activation, the transferred cells entered the intestinal mucosa and became potent antigen-specific killers. Thus, exogenous intact soluble protein entered the major histocompatibility complex class I antigen presentation pathway and induced mucosal cytotoxic T lymphocytes. Moreover, distinct costimulatory requirements for activation of peripheral versus mucosal T cells were noted in that the CD28 ligand, B7-1, was critical for activated mucosal T cell generation but not for activation of peripheral CD8 T cells. The costimulator, B7-2, was required for optimum activation of both populations. Infection with a new recombinant vesicular stomatitis virus encoding ovalbumin induced lytic activity in mucosal as well as peripheral sites, demonstrating an adjuvant effect of inflammatory mediators produced during virus infection. Generation of antiviral cytotoxic T lymphocytes was also costimulation-dependent. The results indicated that induction of peripheral tolerance via antigen administration may not extend to mucosal sites because of distinct costimulatory and inflammatory signals in the mucosa.

Amino Acid Sequence↗

Response surface methodology for optimizing the fermentation medium of Clostridium butyricum.

AIMS: Strains of Clostridium butyricum have been increasingly used as probiotics for both animals and humans. The aim of this study was to develop a growth medium for cultivating C. butyricum ZJUCB using a statistical methodology. METHODS AND RESULTS: Response surface methodology (RSM) was used to evaluate the effects of variables, namely the concentrations of the glucose, pectin, soyabean cake extract, casein, corn steep flour, ammonium sulphate, sodium bicarbonate and the medium initial pH. A fractional factorial design was applied to study the main factors that affected the growth of a probiotic strain of C. butyricum currently preserved in our lab and the central composite experimental design was adopted to derive a statistical model for optimizing the composition of the fermentation medium. The experimental results showed that the optimum fermentation medium for the growth of C. butyricum was composed of 2% glucose (w/v), 0.5% pectin (w/v), 0.2% casein (w/v), 3.98% soyabean cake extract, 0.1% (NH4)2SO4 (w/v), 0.124% NaHCO3 (w/v), 0.37% corn steep flour (w/v), 0.02% MnSO4 H2O (w/v), 0.02% MgSO4 7H2O (w/v) and 0.002% CaCl2 (w/v) at pH 7.5. CONCLUSIONS: After incubating 24 h in the optimum fermentation medium, the populations of the viable organisms were estimated to be 10(9) CFU ml(-1). In the present study, we report the optimization of a growth medium that produced increased yields using statistical approach. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of bacteria as a probiotic is showing increasing potential. The development of a growth medium that has a high yield is an obvious need, and the approach to optimizing a growth medium is innovative.

Bioreactors↗

Non-random mating for selection with restricted rates of inbreeding and overlapping generations.

Minimum coancestry mating with a maximum of one offspring per mating pair (MC1) is compared with random mating schemes for populations with overlapping generations. Optimum contribution selection is used, whereby DeltaF is restricted. For schemes with DeltaF restricted to 0.25% per year, 256 animals born per year and heritability of 0.25, genetic gain increased with 18% compared with random mating. The effect of MC1 on genetic gain decreased for larger schemes and schemes with a less stringent restriction on inbreeding. Breeding schemes hardly changed when omitting the iteration on the generation interval to find an optimum distribution of parents over age-classes, which saves computer time, but inbreeding and genetic merit fluctuated more before the schemes had reached a steady-state. When bulls were progeny tested, these progeny tested bulls were selected instead of the young bulls, which led to increased generation intervals, increased selection intensity of bulls and increased genetic gain (35% compared to a scheme without progeny testing for random mating). The effect of MC1 decreased for schemes with progeny testing. MC1 mating increased genetic gain from 11-18% for overlapping and 1-4% for discrete generations, when comparing schemes with similar genetic gain and size.

Age Factors↗

[10 years teaching general practice for medical students].

Nowadays practice, theory and research in General Medicine can no longer be separated. Besides the definition of the branch of study "medical practioner", standards of achievement and methods of teaching are described. Shortage of medical practioners today results from deficient development and consequences by nonsufficient studies and further education yesterday. Lack in education today is based on non-sufficient research yesterday. Whoever accepts responsibility for the future today has to make the basis by research and education that an optimum care for our population by general practioners will be possible during the coming years.

Curriculum↗

[Incidence of thyroid disorders in children in Hungary].

Author gives information to the home tendencies of incidence of some important thyroid disorders in childhood mainly on the basis of his studies done with his coworkers. Results are compared with the standpoints raised since Chernobyl accident. It is verified on the basis of cca one million neonatal TSH screening that the frequency of congenital hypothyroidism in Hungary corresponds to those of European countries in the last 17 years. Changes connected with Chernobyl has not occurred. It deals with incidence of Graves' disease as the main form of hyperthyroidism relying upon TSH receptor antibody positivity. The yearly distribution of the 176 proved cases shows a slow increasing trend in the same period of time (17 yrs). In this radiation does not play a role. The paper treats of the topic of iodine deficiency with of high priority. Author draws the attention again to the fact that the iodine nutrition in significant part of the population is behind of optimum in harmony with the results of some other national studies also according to their own three thousand urinary iodine tests and more than four thousand thyroid sonographies. This iodine deficiency should be regarded as a potential risk from the viewpoint of radiation hazard! While enlargement of thyroid was often found by sonography, the formation of nodules only rarely in contrast to those of the Chernobyl area. The frequency of thyroiditis, especially in puberty increases too, but the degree of it falls far behind from those of published around of Chernobyl. The incidence of differentiated thyroid carcinoma--according to the available data--moderately increases as well, without any connection between the residence and the geographical distribution of radiation pollution. The epidemiological, clinical, and histological characteristics of the Hungarian children are similar to the so-called sporadic (non-radiation induced) form and different from the cases of the Chernobyl area.

Adolescent↗

[Synchronization of tumor cells with 5-fluorouracil plus uracil and with vinblastine and irradiation of the synchronized cultures. A contribution to combined radio-chemotherapy].

In this article, some arguments are put forward which support the conception of a combined radio-chemotherapy acting by a reversible inhibition of tumor cells with cytostatic drugs in a not cytocidal dose and the following selective killing by irradiation of the cells blocked in a radiosensitive phase. The two cytostatic drugs 5-fluorouracil (FU) and vinblastine (VLB), as inhibitors of DNA synthesis and mitosis, respectively, are tested in vitro both separately and combined in two tumor cell lines of the mouse, i.e. the Ehrlich ascites tumor and the sarcoma S 180. A cell-proliferative and, as far as possible, not cytocidal dose is used because of the inevitable side effects exerted by these drugs on normal tissues. A reversible synchronization of the ascites tumor is achieved even in the young mouse by FU in a dose of 15 ng to 500 ng (applied seven times every two hours), if the synchronization is controlled by applying the antimetabolite together with uracil in an equimolar concentration and then stimulating the growth of the cells inhibited during DNA synthesis by the administration of thymidine. The statistical analysis of dose-effect curves after X-ray irradiation shows an increased radiosensitivity of the synchronized cell population, provided that the optimum moment had been chosen for the irradiation.

Animals↗

Influenza vaccine: preliminary statement. Recommendation of the Public Health Service Advisory Committee on Immunization Practices.

The primary influenza vaccine for 1978-79 will be an inactivated trivalent preparation of antigens representative of the three currently prevalent influenza viruses. A monovalent vaccine will also be produced if needed for optimum immunization of any population group. Annual vaccination is recommended for persons of all ages who have various chronic conditions. Physicians should evaluate pregnant women for influenza immunization according to the criteria applied to other persons.

Female↗

Yellow fever vaccination: how much is enough?

In recent years, a growing number of serious adverse events (including deaths) associated with the yellow fever (YF) vaccine has been reported. If YF vaccination were incorporated in routine programs, administered to children, the risk of deaths from this vaccine would be minimized provided that mortality of children vaccinated below 1 year were negligible. However, in affected areas the vaccine is administered to all age groups. This poses a dilemma to public health authorities - what proportion of a population subject to low risk of YF outbreaks should be vaccinated in order to minimize the total number of serious adverse events (including deaths) due both to natural infection and vaccination? In other words, how much vaccination is safe? Our results suggest that, depending on the age-specific rates of developing vaccine-induced serious adverse events and the risk of yellow fever outbreaks, the optimum proportion to vaccinate may be lower than the proportion that would prevent an epidemics or even be zero. We also show that the vaccine should not be applied to individuals older than 60 years of age because the risk of serious adverse events (including deaths) is higher for that age class. Our work is instrumental to the discussion on the optimum strategy to vaccinate affected populations against yellow fever. Therefore, the aim of this work is to estimate the optimum proportion to vaccinate against YF taking into account the risks of serious adverse events associated with both the vaccine and natural infection.

Adolescent↗

[Optimum number of mixed peripheral blood samples by membrane filtration technique for mass blood survey of filariasis].

The membrane filtration technique has been used widely in the evaluation of effect of control and survey of filariasis. The present study was made to explore an optimum number of mixed peripheral blood samples and a mathematical model of work load for this method in surveying filariasis. By analysing the correlation between the microfilaremia rate and the optimum number of mixed peripheral blood samples and applying the theory of Binomial Distribution or Poisson Distribution, the authors reckoned a table for estimating the number of filariasis cases in villages with different microfilarial rates and different population as well as the optimum number of mixed peripheral blood samples.

Animals↗

Optimal population size and endogenous growth.

"Many applications in economics require the selection of an objective function which enables the comparison of allocations involving different population sizes. The two most commonly used criteria are the Benthamite and the Millian welfare functions, also known as classical and average utilitarianism, respectively. The former maximizes total utility of the society and thus represents individuals, while the latter maximizes average utility and so represents generations. Edgeworth (1925) was the first to conjecture, that the Benthamite principle leads to a larger population size and a lower standard of living.... The purpose of this paper is to examine Edgeworth's conjecture in an endogenous growth framework in which there are interactions between output and population growth rates. It is shown that, under conditions that ensure an optimum, the Benthamite criterion leads to smaller population and higher output growth rates than the Millian."

Demography↗