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At least 343 records · Page 19Linked to original sources
PubMed2000

Compensating for our load of mutations: freezing the meltdown of small populations.

We have investigated the reduction of fitness caused by the fixation of new deleterious mutations in small populations within the framework of Fisher's geometrical model of adaptation. In Fisher's model, a population evolves in an n-dimensional character space with an adaptive optimum at the origin. The model allows us to investigate compensatory mutations, which restore fitness losses incurred by other mutations, in a context-dependent manner. We have conducted a moment analysis of the model, supplemented by the numerical results of computer simulations. The mean reduction of fitness (i.e., expected load) scaled to one is approximately n/(n+2Ne), where Ne is the effective population size. The reciprocal relationship between the load and Ne implies that the fixation of deleterious mutations is unlikely to cause extinction when there is a broad scope for compensatory mutations, except in very small populations. Furthermore, the dependence of load on n implies that pleiotropy plays a large role in determining the extinction risk of small populations. Differences and similarities between our results and those of a previous study on the effects of Ne and n are explored. That the predictions of this model are qualitatively different from studies ignoring compensatory mutations implies that we must be cautious in predicting the evolutionary fate of small populations and that additional data on the nature of mutations is of critical importance.

Animals↗
PubMed1995

Comparative population structuring of molecular and allozyme variation of Drosophila melanogaster Adh between Europe, west Africa and east Africa.

Restriction enzyme molecular variation in Drosophila melanogaster Adh was compared between three natural populations from Europe, West Africa and East Africa. The frequency distribution of silent variation in the slow allele was compatible with the neutral model in all three samples. The number of haplotypes in East Africa was significantly higher than in the other two populations. The largest divergence, as measured by Fst, was between the East African population and a group made up from the West African, the European, and previously studied American populations. We suggest that a split first occurred within African populations at least 44000 years ago. European populations separated from West Africa more recently, between the last glacial maximum and the post-glacial optimum, 18,000 to 8,000 years ago. We suggest that this species was domesticated recently relative to human evolution, possibly with the advent of agriculture. Population differentiation with respect to the two allozymes, fast and slow, does not follow the geographical pattern of silent variation. It opposes European to both African populations, and probably results from selection for adaptation to alcohol in recent temperate populations.

Africa↗
PubMed1996

Population evolution on a multiplicative single-peak fitness landscape.

A theory for evolution of either gene sequences or molecular sequences must take into account that a population consists of a finite number of individuals with related sequences. Such a population will not behave in the deterministic way expected for an infinite population, nor will it behave as in adaptive walk models, where the whole of the population is represented by a single sequence. Here we study a model for evolution of population in a fitness landscape with a single fitness peak. This landscape is simple enough for finite size population effects to be studied in detail. Each of the N individuals in the population is represented by a sequence of L genes which may either be advantageous or disadvantageous. The fitness of an individual with k disadvantageous genes is Wk = (1-s)k, where s determines the strength of selection. In the limit L-->infinity, the model reduces to the problem of Muller's Ratchet: the population moves away from the fitness peak at a constant rate due to the accumulation of disadvantageous mutations. For finite length sequences, a population placed initially at the fitness peak will evolve away from the peak until a balance is reached between mutation and selection. From then on the population will wander through a spherical shell in sequence space at a constant mean Hamming distance from the optimum sequence. We give an approximate theory for the way depends on N, L, s, and the mutation rate u. This is found to agree well with numerical simulation. Selection is less effective on small populations, so increases as N decreases. Our simulations also show that the mean overlap between gene sequences separated by a time of t generations is of the form Q(t) = Q infinity + (Q0-Q infinity)exp(-2ut), which means that the rate of evolution within the spherical shell is independent of the selection strength. We give a simplified model which can be solved exactly for which Q(t) has precisely this form. We then consider the limit L-->infinity keeping U = uL constant. We suppose that each mutation may be favourable with probability p, or unfavourable with probability 1-p. We show that for p less than a critical value pc, the population decreases in fitness for all values of U, whereas for pc < p < 1/2, the population increases in fitness for small U and decreases in fitness for large U. In this case there is an optimum non-zero value of U at which the fitness increases most rapidly, and natural selection will favour species with non-zero mutation rates.

Animals↗
PubMed1985

Expected time for random genetic drift of a population between stable phenotypic states.

Natural selection and random genetic drift are modeled by using diffusion equations for the mean phenotype of a quantitative (polygenic) character in a finite population with two available adaptive zones or ecological niches. When there is appreciable selection, the population is likely to spend a very long time drifting around the peak in its original adaptive zone. With the mean phenotype initially anywhere near the local optimum, the expected time until a shift between phenotypic adaptive peaks increases approximately exponentially with the effective population size. In comparison, the expected duration of intermediate forms in the actual transition between adaptive peaks is extremely short, generally below the level of resolution in the fossil record, and increases approximately logarithmically with the effective population size. The evolutionary dynamics of this model conform to the pattern of current paleontological concepts of morphological "stasis" and "punctuated equilibria."

Biological Evolution↗
PubMed1984

Hospital bed planning in Canada: a survey analysis.

The need to plan health and especially hospital care delivery systems is becoming more critical in this period of severe financial constraints and even cutbacks of services. This article reports on a survey of hospital planning norms and bed requirements methodologies in Canada conducted in 1977 and 1980. The comparison and assessment of approaches to bed need determination in the Canadian provinces, together with some recommendations, are preceded by a review of basic hospital planning methods and their use in a number of selected countries. The literature review and the analysis conducted reveal that the "formula method" (beds per 1000 population) is the most common approach used to define and to allocate the "optimum" number of beds in the countries reviewed and in Canada. Despite its shortcomings, this method appears to have many advantages (e.g., simplicity, equity, flexibility). In general, provincial authorities use similar factors in the calculation of the number of beds to be provided, the most important ones being the size of the projected geographic population or population served by age groups. The acute care bed guidelines in Canada range from 3.5 per 1000 population in southern Ontario to 5.0 in Saskatchewan and Alberta. Extended care bed guidelines are much more spread between provinces. The analysis underlines the difficulties faced by the planner and the researcher in comparing bed guidelines due to significant definition and content differences between provinces. It finally leads to the observation that hospital planning remains arbitrary and appears to be more designed to ration the supply of services and to contain overall expenditures than to really try to meet the "need" of the population for hospital services.

Bed Occupancy↗
PubMed1999

Helicobacter pylori: optimum diagnosis and test of cure.

The fact that about 50% of the world's population is infected with Helicobacter (H.) pylori and the important role that this bacterium plays in public health have been important incentives in the search for accurate diagnostic methods. A large number of invasive and non-invasive methods have been used to diagnose H. pylori infection. Each method has its advantages and disadvantages and each practitioner should choose the best diagnostic method according to the facilities available. Non-invasive tests for the diagnosis of H. pylori infection are largely used in clinical practice and in management of patients with gastroduodenal disease. Serology is the most widespread test but its use is not advised in the post-treatment follow-up. The Urea Breath Test is a simple, safe and highly accurate method ideal for evaluating the short-term follow-up of H. pylori eradication after therapy.

Breath Tests↗
PubMed2003

Population stratification and spurious allelic association.

Great efforts and expense have been expended in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, technology for detection and scoring of single nucleotide polymorphisms (SNPs) has undergone rapid development, extensive catalogues of SNPs across the genome have been constructed, and SNPs have been increasingly used as a means for investigation of the genetic causes of complex human diseases. For many diseases, population-based studies of unrelated individuals--in which case-control and cohort studies serve as standard designs for genetic association analysis--can be the most practical and powerful approach. However, extensive debate has arisen about optimum study design, and considerable concern has been expressed that these approaches are prone to population stratification, which can lead to biased or spurious results. Over the past decade, a great shift has been noted, away from case-control and cohort studies, towards family-based association designs. These designs have fewer problems with population stratification but have greater genotyping and sampling requirements, and data can be difficult or impossible to gather. We discuss past evidence for population stratification on genotype-phenotype association studies, review methods to detect and account for it, and present suggestions for future study design and analysis.

Alleles↗
PubMed1975

Occurence of lactose-negative mutants in chemostat cultures of lactic streptococci.

Batch and chemostat cultures of Streptococcus cremoris HP and Streptococcus lactis 829 were examined for lactose-hegative (lac-)mutants on indicator agar. In batch cultures, S. cremoris HP gave less than 1% of the total count as lac- colonies while S. lactis 829 consistently contained about 15% of the total as lac- colonies. In chemostat cultures of S. cremoris HP in 2% skim milk containing casamino acids and yeast extract (0.1% each), the percentage of lac- colonies increased markedly when the temperature of growth was 18 degrees C but not when the temperature of growth was 25 degrees C. The percentage of lac- colonies in chemostat cultures in the skim milk medium at 25 degrees C was about the same as that in batch cultures. On the other hand, when chemostat cultures of S. lactis 829 in the skim milk medium were grown at several temperatures between 18 and 33 degrees C, the percentage of lac- colonies was markedly lower than that found in batch cultures of this organism. Cultivation of S. cremoris HP in chemostats with yeast extract-glucose broth at low temperature (18 degrees C) resulted in a selection of cells giving lac- colonies and atypical (small) lac+ colonies. The results show that cultivation of S. cremoris HP and S. lactis 829 in chemostats sometimes gave rise to altered populations. Conditions causing a change in one organism did not necessarily cause a similar change in the other. The results indicate that the successful propagation of lactic streptococci in chemostats for use as starter cultures in the dairy industry will require the careful establishment of optimum conditions for every strain so as to minimize the possible selection of undesirable populations.

Agar↗
PubMed2005

Waist circumference criteria for the diagnosis of abdominal obesity are not applicable uniformly to all populations and ethnic groups.

Determination of cutoff points of waist circumference is of paramount importance for prevention, optimum management, and prognostication of obesity, the metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. Heterogeneity of composition of abdominal tissues, in particular adipose tissue and skeletal muscle, and their location-specific and changing relations with metabolic factors and cardiovascular risk factors in different ethnic groups do not allow a simple definition of abdominal obesity that could be applied uniformly. In particular, Asians appear to have higher morbidity at lower cutoff points for waist circumference than do white Caucasians. International health agencies that deal with obesity (World Health Organization, International Obesity Task Force) should take cognizance of these data and consider formulating new cutoff points for waist circumference to define abdominal obesity for Asian populations.

Abdominal Fat↗
PubMed2006

Intra-specific genetic relationship analyses of Elaeagnus angustifolia based on RP-HPLC biochemical markers.

Elaeagnus angustifolia Linn. has various ecological, medicinal and economical uses. An approach was established using RP-HPLC (reversed-phase high-performance liquid chromatography) to classify and analyse the intra-specific genetic relationships of seventeen populations of E. angustifolia, collected from the Xinjiang areas of China. Chromatograms of alcohol-soluble proteins produced by seventeen populations of E. angustifolia, were compared. Each chromatogram of alcohol-soluble proteins came from a single seed of one wild plant only. The results showed that when using a Waters Delta Pak. C18, 5 microm particle size reversed phase column (150 mm x 3.9 mm), a linear gradient of 25%-60% solvent B with flow rate of 1 ml/min and run time of 67 min, the chromatography yielded optimum separation of E. angustifolia alcohol-soluble proteins. Representative peaks in each population were chosen according to peak area and occurrence in every seed. The converted data on the elution peaks of each population were different and could be used to represent those populations. GSC (genetic similarity coefficients) of 41% to 62% showed a medium degree of genetic diversity among the populations in these eco-areas. Cluster analysis showed that the seventeen populations of E. angustifolia could be divided into six clusters at the GSC=0.535 level and indicated the general and unique biochemical markers of these clusters. We suggest that E. angustifolia distribution in these eco-areas could be classified into six variable species. RP-HPLC was shown to be a rapid, repeatable and reliable method for E. angustifolia classification and identification and for analysis of genetic diversity.

Chromatography, High Pressure Liquid↗
PubMed1991

Rumen digestive physiology and microbial ecology.

The rumen is a dynamic, continuous fermentation compartment that provides a suitable environment for a variety of species of anaerobic bacteria, protozoa, and fungi. These microorganisms have a complex series of interactions with the feeds supplied to the host, with some using particulate matter as both sources of nutrients and sites of sequestration to avoid being washed from the rumen by the rapid flow of fluids. Because of the ability to use soluble nutrients and to reproduce rapidly, other microbes associate primarily with the liquid phase of the rumen contents. Due to the metabolic activity of all microbial populations, feeds are converted to microbial matter and fermentation end products, which serve as nutrients for the ruminant. Optimum feed utilization by ruminants is dependent on achieving maximum rumen fermentation and flow of microbial protein to the duodenum. At this time, it is clear that the major nutrients required by the microbial populations include both fibrous and nonfibrous sources of carbohydrates and nitrogen in the form of ammonia, amino acids, and peptides. In spite of five decades of research, the exact quantities and sources of these nutrients that will result in optimum rumen fermentation rates and microbial yields are only partially known.

Animals↗
PubMed1992

Does frequency-dependent selection optimize fitness?

In evolutionary biology, the axiom that natural selection tends ideally to maximize inclusive fitness of the individual or some other suitable quantity is often advanced (Cody, 1974; Maynard Smith, 1978; Krebs & McCleery, 1984; Houston et al., 1988). Moreover, the evolutionists generally distinguish two situations (Dawkins, 1980; Maynard Smith, 1982): one in which fitness is independent of the frequency of the phenotypes present in the population (frequency-independent selection), and one in which it does depend on this frequency (frequency-dependent selection). This led some authors such as Parker (1984), and more recently Parker & Maynard Smith (1990), to consider "a 2-speed optimization": frequency-independent selection should lead to a "simple optimum" at the end of the selective process, since all the individuals should have the same strategy and the mean fitness of the population should be maximized; frequency-dependent selection, formulated in terms of the theory of games, should lead to a "competitive optimum" even though the "evolutionary stable strategy" (or "ESS"; Maynard Smith & Price, 1973) characterizing the equilibrium "is not the strategy that maximizes fitness in a population sense" (Parker & Maynard Smith, 1990: 30). Our aim in this short communication is to criticize the concept of "competitive optimum" by Parker & Maynard Smith, as well as the general ability of natural selection to "maximize fitness", even in "phenotypic models" (Lloyd, 1977). These models, devoid of genetic constraints since each strategist is assumed to reproduce its own kind, are especially suitable for examining the ideal effect of natural selection.

Animals↗
PubMed1994

Optimum parameters in a model for tumour control probability including interpatient heterogeneity.

A model for computing tumour control probability (TCP) is studied which embodies a dependence on the size of the irradiated volume, the density of clonogenic cells and the dose received, together with the alpha and beta parameters of the linear quadratic model of cell kill. The model can be used to describe situations where both the dose and the clonogenic cell densities are inhomogeneously distributed; however there is still uncertainty about its radiobiological parameters and the author aims to establish parameters for four types of tumour. In its simplest form, when the volumes are spherical, the clonogenic cell density is considered constant throughout the volume and the dose is uniform, the model has been used (by D.J. Brenner, 1993) to predict the radiobiological parameter alpha which allows the model to best fit the observed clinical data for four types of tumour. Here a new set of fits to the data presented by Brenner is constructed using a model which includes the distribution of radiosensitivity across a heterogeneous patient population. It is shown that this leads to a different set of optimum radiobiological parameters when the clonogenic cell density is of the order of 107 cells cm-3.

Dose Fractionation, Radiation↗
PubMed2003

Treatment of Lennox-Gastaut syndrome.

BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and personality disorders. It occurs more frequently in males and onset is usually before the age of eight with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (for example hyperactivity, aggressiveness and autistic tendencies)and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time. OBJECTIVES: To compare the effects of pharmaceutical therapies used to treat Lennox-Gastaut syndrome in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialed (often as add-on therapy). SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (March 2003), MEDLINE (1966 to March 2003) and EMBASE (1980 to March 2003). In addition, we contacted pharmaceutical companies and colleagues in the field to ascertain any unpublished/ongoing studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with Lennox-Gastaut syndrome. DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (eg drop attacks), adverse effects and mortality. MAIN RESULTS: We found five RCTs, but were unable to perform any sort of meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes. REVIEWER'S CONCLUSIONS: The optimum treatment for Lennox-Gastaut syndrome remains uncertain and no study to date has shown any one drug to be highly efficacious; lamotrigine, topiramate and felbamate may be helpful as add-on therapy. Until further research has been undertaken clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

Age of Onset↗
PubMed1978

An effect of cell-cycle position on ultraviolet-light-induced mutagenesis in Chinese hamster ovary cells.

Using synchronous populations obtained by selectively detaching mitotic cells from cultures grown in monolayer, we demonstrate here that Chinese hamster ovary (CHO) cells exhibit a differential sensitivity to mutation induction by UV as a function of position in the cell cycle. When mutation induction to 6-thioguanine (TG) resistance is monitored, several maxima and minima are displayed during cell-cycle traverse, with a major maximum occurring in early S phase. Although cells in S phase are more sensitive to UV-mediated cell lethality than those in G1 or G2/M phases, there is not a strict correlation with induced mutation frequency. Fluence-response curves obtained at several times during the cell cycle yield Dq values approximating 6 J/m2. The primary survival characteristic which varies with cell cycle position is D0, ranging from 2.5 J/m2 at 6 h after mitotic selection to 5.5 J/m2 at 11 h afterward. Based on studies with asynchronous, logarithmically growing populations, as well as those mitotically selected to be synchronous, the optimum phenotypic expression time for induced TG resistance is 7--9 days and is essentially independent of both UV fluence and position in the cell cycle. All isolated mutants have altered hypozanthine-guanine phosphoribosyl transferase (HGPRT) activity, and no difference in the residual level of activity was detected among isolated clones receiving UV radiation during G1, S, or late S/G2 phases of the cell cycle. Changes in cellular morphology during cell-cycle traverse do not contribute to the differential susceptibility to UV-induced mutagenesis.

Cell Cycle↗
PubMed1999

Optimum dental radiography in bone marrow transplant patients.

OBJECTIVE: The purpose of this study was to establish an optimum radiographic examination regimen for patients undergoing bone marrow transplantation. Two radiographic examinations were compared: the panoramic radiograph and the full mouth series of radiographs. STUDY DESIGN: A prospective analysis of 65 consecutive patients undergoing bone marrow transplantation was undertaken. All patients were examined through use of both panoramic and full mouth series intraoral radiographs, including bitewings. Significant findings were recorded and compared by means of paired t test analysis for parametric data, such as caries, periapical inflammation and subgingival calculus, and by means of McNemar's test for nonparametric data, such as the presence or absence of severe periodontal disease. RESULTS: Acquired findings, such as caries, periodontal disease, and clinically significant faulty restorations, were detected more frequently from the full mouth series (P < .05). There was no significant difference in the detection of periapical pathosis. In 8 of 65 patients, clinically significant information, such as evidence of impacted wisdom teeth, neoplasms, and multiple myeloma, was better detected from the panoramic radiographs. CONCLUSIONS: The results suggest a combination of both modalities as the optimum means of radiologic survey in this "high-risk" patient population.

Adolescent↗