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PubMed2003

Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.

Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.

Animals↗
PubMedDate not supplied

Optimal selection on two quantitative trait loci with linkage.

A mathematical approach to optimize selection on multiple quantitative trait loci (QTL) and an estimate of residual polygenic effects was applied to selection on two linked or unlinked additive QTL. Strategies to maximize total or cumulative discounted response over ten generations were compared to standard QTL selection on the sum of breeding values for the QTL and an estimated breeding value for polygenes, and to phenotypic selection. Optimal selection resulted in greater response to selection than standard QTL or phenotypic selection. Tight linkage between the QTL (recombination rate 0.05) resulted in a slightly lower response for standard QTL and phenotypic selection but in a greater response for optimal selection. Optimal selection capitalized on linkage by emphasizing selection on favorable haplotypes. When the objective was to maximize total response after ten generations and QTL were unlinked, optimal selection increased QTL frequencies to fixation in a near linear manner. When starting frequencies were equal for the two QTL, equal emphasis was given to each QTL, regardless of the difference in effects of the QTL and regardless of the linkage, but the emphasis given to each of the two QTL was not additive. These results demonstrate the ability of optimal selection to capitalize on information on the complex genetic basis of quantitative traits that is forthcoming.

Animals↗
PubMed2026

Impact of genomic selection for disease resistance on the spread of infection in a simulated aquaculture population.

BACKGROUND: In aquaculture, selection for disease resistance is typically based on mortality records from challenge tests performed on relatives of selection candidates. However, commercial success depends on limiting disease transmission, particularly the incidence and severity of outbreaks. It remains unclear whether selecting for lower mortality also reduces disease transmission. Both these outcomes are influenced by three underlying epidemiological host traits: susceptibility, infectivity, and infection-induced mortality. This simulation study evaluated the impact of genomic selection against mortality on disease transmission in a salmon population exposed to a pathogen with a fast transmission rate. METHODS: Mortality was assumed to be recorded on sibs of selection candidate, either as binary dead/alive status or as time to death during cohabitation/bath challenge tests. Phenotypes were simulated using a stochastic compartmental Susceptible-Infected-Removed epidemiological model, with genetic variation for the three underlying traits. Scenarios were explored by varying the genetic correlations between the three underlying traits. Challenge test designs varied in the number of groups, group sizes, and family distribution across groups. For comparison, a reference scenario with direct selection on the underlying traits was included. Genomic selection was applied over 10 discrete generations, and its impact on disease transmission was assessed using the basic reproductive ratio (R0). RESULTS: When selection was based on dead/alive status, R0 was highly sensitive to both the genetic correlations between the three underlying traits and the challenge test design. In contrast, selection based on time to death consistently reduced R0 across all scenarios (often to below 1 within four generations), regardless of trait correlations or test design. Selection on time to death primarily produced fish with reduced susceptibility to infection, while selection on dead/alive status produced fish with increased resistance and endurance to infection, delaying onset of infection or death without necessarily limiting transmission. Direct selection on the underlying epidemiological traits was the most efficient approach to reduce both mortality and transmission. CONCLUSIONS: Genomic selection for disease resistance, when measured as time to death in cohabitation or bath challenge tests conducted until mortality naturally levels off, reduces both mortality and disease spread. Breeding programs may benefit from challenge test designs that enable estimation of genetic parameters for the underlying traits affecting disease transmission and survival.

Animals↗
PubMed2001

Selection for lean growth efficiency in Duroc pigs influences pork quality.

A unique line of Duroc pigs was established by intensive selection for increased lean growth efficiency. The objective of this study was to determine the influence of this selection strategy on fresh pork quality traits. Two lines of Duroc pigs originating from the same foundation herd were evaluated. One line was selected for lean growth efficiency over five generations (Select line), and the other was a contemporary line maintained from the foundation herd (Control line). All pigs in the trial tested negative for the halothane gene. Selection for lean growth efficiency resulted in improved lean gain, carcass lean, increased loin eye area, and less overall carcass fat. The Select line had significantly lower subjective firmness scores in longissimus and significantly greater amounts of moisture and protein lost as measurable drip in longissimus, semimembranosus, and semitendinosus. There were no differences in subjective color scores or in Hunter L, a, and b values between lines. No selection line differences were observed in glycolytic potential or ultimate pH. The longissimus and the semitendinosus exhibited significantly lower early postmortem pH values in Select line pigs. Warner-Bratzler shear values were higher for Select line longissimus chops. Degradation of troponin-T was decreased in the Select line longissimus samples. This result suggests that reduced degradation of myofibrillar proteins may be associated with increased moisture and protein lost during storage. This research points out that elimination of the halothane gene will solve some but not all of the genetically influenced pork quality problems faced by the industry. The Select line of pigs appears to be more prone to producing pork that is soft and exudative, indicating a link between soft and exudative pork and some genetic selection strategies may exist. Therefore, it appears that selection for some economically important traits, such as feed efficiency or increased lean growth in the absence of the halothane gene, may compromise pork quality.

Animals↗
PubMed2001

Direct and correlated responses to two-stage selection for ovulation rate and number of fully formed pigs at birth in swine.

Our objectives were to estimate responses and genetic parameters for ovulation rate, number of fully formed pigs at birth, and other production traits following two-stage selection for increased ovulation rate and number of fully formed pigs. Eight generations of selection were practiced in each of two lines. One selection line was derived from a line that previously selected eight generations for an index to increase ovulation rate and embryonic survival (the IOL pigs). The other selection line was derived from the unselected control line of the index selection experiment (the COL pigs). The control line (C) was continued with random selection. Due to previous selection, Line IOL had greater ovulation rate (4.24 +/- 0.38 and 4.14 +/- 0.29 ova) and litter size (1.97 +/- 0.39 and 1.06 +/- 0.38 pigs) at Generation 0 of two-stage selection than did Lines COL and C. In Stage 1, all gilts from 50% of the largest litters were retained. Approximately 50% of them were selected for ovulation rate in Stage 2. Gilts selected for ovulation rate were mated to boars selected from the upper one-third of the litters for litter size. At Generations 7 and 8, differences in mean EBV for ovulation rate and litter size between Lines IOL and C were 6.20 +/- 0.29 ova and 4.66 +/- 0.38 pigs; differences between Lines COL and C were 2.26 +/- 0.29 ova and 2.79 +/- 0.39 pigs; and differences between Lines IOL and COL were 3.94 +/- 0.26 ova and 1.86 +/- 0.39 pigs. Regressions of line mean EBV on generation number were 0.27 +/- 0.07 ova and 0.35 +/- 0.06 pigs in Line IOL; 0.30 +/- 0.06 ova and 0.29 +/- 0.05 pigs in Line COL; and 0.01 +/- 0.07 ova and 0.02 +/- 0.05 pigs in Line C. Correlated responses were decreased age at puberty and increased number of pigs born alive, number of mummified pigs, prenatal loss, and individual and litter birth weight. Two-stage selection for ovulation rate and number of pigs per litter is a promising procedure to improve litter size in swine.

Animal Husbandry↗
PubMed1996

Short-term selection for four-week body weight in Japanese quail.

Japanese quail have been utilized as a research animal to establish genetic relationships that may be present in other poultry species. In this presentation, short-term selection experiments were reviewed. Selection intensity appeared to be the most effective in improving BW when selection experiments were compared on a response per generation basis; however, when generation interval was reduced, the response per year was superior despite lower selection intensities for lines selected the same number of generations. Correlated responses over 30 generations of divergent selection for 4-wk BW indicated that selection had a negative effect on fitness traits, including egg number and fertility. Traits such as follicle and egg weight and BW at the beginning of and after a 120-d laying period were positively correlated with BW during the growth period. The early response of quail lines selected for increased BW at 10, 17, 28, and 40 d of age indicate that the later selection is applied the greater the selection response at maturity. In fact, lines selected at young ages were competitive with late-selected lines only to the point at which selection occurred.

Aging↗
PubMed1998

[Selective structure of the gene pool. III. Technology of determination from F(ST)-statistics using numerical resampling].

The selection pressure on the ith gene was determined on the basis of the heterogeneity of interpopulation diversity FST(i), assumpting that the significant deviation of FST(i) (observed differentiation of the ith gene) from Fe (selectively neutral differentiation) indicates selection. A selectively neutral variation Fe was estimated from the mean FST, averaged over the total set of genes. Since the validity of the equation FST approximately Fe = (4NeMe + 1)-1 depends on the fulfillment of conditions of the theoretical model as well as on organization of sampling of genes and subpopulations rather than on statistical parameters of the gene sample, an additional correction by boot-strapping is suggested. Simulation of sampling of the gene pool using numerical resampling (10(6) samples from each of the 50 markers) allowed us to characterize the selective structure of the gene pool. This structure consists of the following: one class of selectively neutral genes, NEUTRAL (FST(i) approximately Fe); and two classes of selective genes, LOWER DIFF (FST(i) < Fe) and SUPER DIFF (FST(i) > Fe). Interclass regions N-LOWER and N-SUPER between the classes of neutral and selective genes were defined with the use of bootstrapping. The hypothesis on the presence or absence of selection cannot be formulated with regard to the genes included in the interclass regions. A general trend for all gene pools of the world was revealed: the ratio between the boundary values of selective classes and Fe is constant. On the basis of this, a rapid and simple technique for estimating selective values of genes was developed. The positions of more than 80 immunobiochemical gene markers in the selective structure of six gene pools of the world (Europe, Asia, Africa, Australia, America, and northeastern Eurasia) are presented. The selective structure of five subregions of northeastern Eurasia (Caucasus, Europe, Ural, Siberia, and Central Asia) are characterized as well.

Data Interpretation, Statistical↗
PubMed1999

Sexual selection resulting from extrapair paternity in collared flycatchers.

Extrapair paternity has been suggested to represent a potentially important source of sexual selection on male secondary sexual characters, particularly in birds with predominantly socially monogamous mating systems. However, relatively few studies have demonstrated sexual selection within single species by this mechanism, and there have been few attempts to assess the importance of extrapair paternity in relation to other mechanisms of sexual selection. We report estimates of sexual selection gradients on male secondary sexual plumage characters resulting from extrapair paternity in the collared flycatcher Ficedula albicollis, and compare the importance of this form of sexual selection with that resulting from variation in mate fecundity. Microsatellite genotyping revealed that 15% of nestlings, distributed nonrandomly among 33% of broods (N=79), were the result of extrapair copulations. Multivariate selection analyses revealed significant positive directional sexual selection on two uncorrelated secondary sexual characters in males (forehead and wing patch size) when fledgling number was used as the measure of fitness. When number of offspring recruiting to the breeding population was used as the measure of male fitness, selection on these traits appeared to be directional and stabilizing, respectively. Pairwise comparisons of cuckolded and cuckolding males revealed that males that sired young through extrapair copulations had wider forehead patches, and were paired to females that bred earlier, than the males that they cuckolded. Path analysis was used to partition selection on these traits into pathways via mate fecundity and sperm competition, and suggested that the sperm competition pathway accounted for between 64 and 90% of the total sexual selection via the two paths. The selection revealed in these analyses is relatively weak in comparison with many other measures of selection in natural populations. We offer some explanations for the relatively weak selection detected. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Differential MHC expression requirements for positive selection of separate TCR Vb families.

Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6(+)CD4(+) and Vb10(+)CD4(+) thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13(+)CD8(+) thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea-->NOD-Ea chimeras have an increased positive selection of Vb13(+)CD8(+) cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6(+)CD4(+) cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10(+)CD4(+) cells was restricted to E-expressing thymic epithelium only. For Vb13(+)CD8(+ )cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6(+) CD4(+) cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10(+)CD4(+ )cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.

Animals↗
PubMedDate not supplied

Implementing the Fisher's discriminant ratio in a k-means clustering algorithm for feature selection and data set trimming.

The Fisher's discriminant ratio has been used as a class separability criterion and implemented in a k-means clustering algorithm for performing simultaneous feature selection and data set trimming on a set of 221 HIV-1 protease inhibitors. The total number of molecular descriptors computed for each inhibitor is 43, and they are scaled to lie between 1 and 0 before being subjected to the feature selection process. Since the purpose is to select some of the most class sensitive descriptors, several feature evaluation indices such as the Shannon entropy, the linear regression of selected descriptors on the pKi of selected inhibitors, and a stepwise variable selection program are used to filter them. While the Shannon entropy provides the information content for each descriptor computed, more class sensitive descriptors are searched by both the linear regression and stepwise variable selection procedures. The inhibitors are divided into several different numbers of classes. They are subsequently divided into five classes due to the fact that the best feature selection result is obtained by the division. Most of the good features selected are the topological descriptors, and they are correlated well with the pKi values. The outliers or the inhibitors with less class-sensitive descriptor values computed for each selected descriptor are identified and gathered by the k-means clustering algorithm. These are the trimmed inhibitors, while the remaining ones are retained or selected. We find that 44% or 98 inhibitors can be retained when the number of good descriptors selected for clustering is three. The descriptor values of these selected inhibitors are far more class sensitive than the original ones as evidenced by substantial increasing in statistical significance when they are subjected to both the SYBYL CoMFA PLS and Cerius2 PLS regression analyses.

Journal Article↗
PubMed2000

Comparison of the selectivity of postsynaptic potentials and spike responses in cat visual cortex.

Intracellular recordings were made from neurons in the cat visual cortex (area 17) to compare the orientation and direction selectivities of the output of a cell with those of the input the cell receives. The input to a cell was estimated from the PSPs (postsynaptic potentials) evoked by visual stimulation, and the output estimated from the number of spikes generated during the same responses. For the whole sample, selectivity of the output of cells was significantly higher than selectivity of their input. Upon PSP to spike transformation, the selectivity index was, on average, doubled. However, the degree of the selectivity improvement in individual cells was very different, varying from cases in which highly selective output was created from a poorly selective input and thus selectivity was greatly improved, to little or no improvement in other neurons. The improvement of selectivity was not correlated with resting membrane potential, threshold for action potential generation, background discharge rate or amplitude of optimal PSP response. Further, no systematic difference was found between simple and complex cells in the input-output relations, indicating that the 'tip of the iceberg' effect on shaping the response selectivity was cell specific, but not cell type specific. This supports the notion that multiple mechanisms are responsible for generation of the response selectivity, and that the contribution of any particular mechanism may vary from one cell to the other. The heterogeneity of the input-output relations in visual cortical cells could indicate different functions of cells in the cortical network; some cells are creating selectivity de novo, the function of other neurons probably being repetition and amplification of the selected signal and arrangement of the output of a whole column.

Action Potentials↗
PubMed2005

The resistance ratchet: theoretical implications of cyclic selection pressure.

OBJECTIVES: To investigate the effects of cyclic antibiotic selection pressure on resistance in a simple mathematical model. METHODS: The model assumed that resistance in microbial ecologies changes slowly with changing selection pressure, at a rate proportional to the difference between the current resistance level and the resistance level that would be in equilibrium with current selection pressure. The maximum rate of increase in resistance during periods of increasing selection was assumed to be greater than the maximum rate of decrease during decreased selection. RESULTS: Under a simulated annual cyclic selection pressure variation of 40%, with maximum resistance rise and fall rates of 10 and 0.5%, respectively, resistance rose above the level expected from the mean selection pressure by small ratchet-like increments. Over 50 simulated years, resistance increased to 62%, rather than the 50% expected from the mean level of selection. Welsh community prescribing for a selection of antibiotics showed a seasonal cyclic variation of 13-45%. CONCLUSIONS: The intuitive assumption that cyclic selective pressure would produce resistance levels commensurate with the mean selection pressure was contradicted; rather resistance drifted towards a level commensurate with maximum selection pressure. If the ratchet effect exists in reality, it may produce unexpected excess resistance, particularly in the community for antibiotics used in respiratory infection, where cycling is pronounced, or in ITU antibiotic rotation. It should be most pronounced for resistance systems with strong asymmetry between rates of adaptation under rising and falling selection pressure. Non-linear dynamic systems in physics and ecology are notorious for producing counter-intuitive effects; resistance epidemiology may be similar.

Anti-Bacterial Agents↗
PubMed2006

Development and application of a positive-negative selectable marker system for use in reverse genetics in Plasmodium.

A limitation of transfection of malaria parasites is the availability of only a low number of positive selectable markers for selection of transformed mutants. This is exacerbated for the rodent parasite Plasmodium berghei as selection of mutants is performed in vivo in laboratory rodents. We here report the development and application of a negative selection system based upon transgenic expression of a bifunctional protein (yFCU) combining yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT) activity in P.berghei followed by in vivo selection with the prodrug 5-fluorocytosine (5-FC). The combination of yfcu and a positive selectable marker was used to first achieve positive selection of mutant parasites with a disrupted gene in a conventional manner. Thereafter through negative selection using 5-FC, mutants were selected where the disrupted gene had been restored to its original configuration as a result of the excision of the selectable markers from the genome through homologous recombination. This procedure was carried out for a Plasmodium gene (p48/45) encoding a protein involved in fertilization, the function of which had been previously implied through gene disruption alone. Such reversible recombination can therefore be employed for both the rapid analysis of the phenotype by targeted disruption of a gene and further associate phenotype and function by genotype restoration through the use of a single plasmid and a single positive selectable marker. Furthermore the negative selection system may also be adapted to facilitate other procedures such as 'Hit and Run' and 'vector recycling' which in principle will allow unlimited manipulation of a single parasite clone. This is the first demonstration of the general use of yFCU in combination with a positive selectable marker in reverse genetics approaches and it should be possible to adapt its use to many other biological systems.

Animals↗
PubMed2003

The Lenke classification of adolescent idiopathic scoliosis: how it organizes curve patterns as a template to perform selective fusions of the spine.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVES: To analyze how the Lenke classification of adolescent idiopathic scoliosis provides a template of specific curve patterns that may be appropriate to perform selective fusion of the spine. METHODS: A new triad classification system of adolescent idiopathic scoliosis has been developed. It consists of a curve type, a lumbar spine modifier (A, B, C), and a sagittal thoracic modifier (-, N, +). A selective fusion is termed when both the thoracic and thoracolumbar/lumbar curves deviate completely from the midline, but only the major curve (largest Cobb measurement) is fused, leaving the minor curve unfused and mobile. In this manner, selective thoracic fusions of the spine are potentially indicated for major main thoracic/minor lumbar curves (Types 1C and potentially 2C and 3C patterns) when the lumbar apex deviates off the center sacral vertical line. Conversely, selective thoracolumbar/lumbar fusions may be indicated for major thoracolumbar/lumbar-minor main thoracic curves, when the thoracic apex lies off the C7 plumbline (Type 5C and potentially 6C patterns). Importantly, additional analysis of ratios of structural characteristics between the main thoracic and thoracolumbar/lumbar curves are necessary to predict when a successful selective main thoracic or thoracolumbar/lumbar fusion will be feasible. Lastly, the clinical appearance of the patient's truncal alignment is essential to confirm the aspirations of performing a selective spinal fusion. RESULTS: Successful selective thoracic fusion of 1C (n = 36) and 2C (n = 8) curves have been performed in 44 consecutive patients with adolescent idiopathic scoliosis. The average thoracic curve was 61 degrees before surgery and 39 degrees at final follow-up. The average preoperative lumbar curve was 48 degrees, decreasing to 32 degrees postoperatively. A group of 21 consecutive patients with Type 5C or 6C major thoracolumbar/lumbar-minor main thoracic curves underwent a selective thoracolumbar/lumbar fusion. The average preoperative thoracolumbar/lumbar curve was 56 degrees corrected to 22 degrees at the 2-year follow-up. The average minor main thoracic curve preoperative was 38 degrees, with spontaneous correction to 28 degrees at 2 years postoperative. DISCUSSION: Selective thoracic or thoracolumbar/lumbar fusion can be successfully performed in a variety of adolescent idiopathic scoliosis curve patterns. Careful attention to the preoperative Lenke curve classification, analysis of structural characteristics between the planned instrumented and noninstrumented regions of the spine, as well as a documented clinical examination that confirms the planned instrumented and fused regions of the spine to be the most clinically prominent are essential features to determine before surgery. No patients undergoing selective thoracic fusion have required extension of the fusion to the lumbar spine, whereas one patient with a selective thoracolumbar fusion required extension of the fusion up to include the thoracic spine due to continued thoracic progression with growth. CONCLUSIONS: Selective thoracic or thoracolumbar/lumbar fusions of the major curve can be successfully performed even when the minor curve completely deviates from the midline, based on the Lenke classification system, the analysis of structural criteria between the planned fused and unfused regions of the spine, and the clinical examination of the patient. Selective fusions, when successfully performed, will optimize mobile segments of the spine in patients with adolescent idiopathic scoliosis.

Adolescent↗
PubMed2000

Disease, frequency-dependent selection, and genetic polymorphisms: experiments with stripe rust and wheat.

Pathogens have the potential to maintain genetic polymorphisms by creating frequency-dependent selection on their host. This can occur when a rare host genotype is less likely to be attacked by a pathogen (frequency-dependent disease attack) and has higher fitness at low frequency (negative frequency-dependent selection). In this study, we used wheat genotypes that were susceptible to different races of the pathogen Puccinia striiformis to test whether disease created frequency-selection on its host and whether such selection could maintain polymorphisms for resistance genes in the wheat populations. Four different two-way mixtures of wheat genotypes were planted at different frequencies in both the presence and absence of disease. Disease created frequency-dependent selection on its host in some populations. Unknown factors other than disease also created frequency-dependent selection in this system because, in some instances, rare genotype advantage was observed in the absence of disease. Although the pathogen created frequency-dependent selection on its host, this selection was not sufficient to maintain genetic polymorphism in the host populations. In all cases where frequency-dependent selection occurred only in the diseased plots, one of the two genotypes was predicted to dominate in the population and the same genotype was predicted to dominate in both the presence and absence of disease. Only in cases where frequency-dependent selection was not caused by disease was there evidence that genetic polymorphisms would be maintained in the population. The frequency-dependent selection described in this study is a consequence of epidemiological effects of disease and differs from the time-lagged frequency-dependent selection resulting from coevolution between hosts and parasites. The impact of this direct frequency-dependent selection on the maintenance of genetic polymorphisms in the host population is discussed.

Fungi↗
PubMed2004

Impact of selective cyclooxygenase-2 inhibitors on anti-ulcer medication and non-steroidal anti-inflammatory drug use in patients with rheumatic disease.

BACKGROUND: Anti-inflammatory medications are the most common treatment for rheumatic disease in Australia. Recent years have seen large increases in the use of selective cyclooxygenase-2 (COX-2) inhibitors. Predictors of use, costs and benefits of the new medications have not been evaluated. AIMS: To determine trends in selective COX-2 inhibitor, non-steroidal anti-inflammatory drug (NSAID) and anti-ulcer medication (AUM) prescription following the introduction of selective COX-2 inhibitors; to determine predictors of selective COX-2 inhibitor, NSAID and AUM prescribing and to perform a limited evaluation of the costs and benefits associated with the introduction of selective COX-2 inhibitors. METHODS: Groups of consecutive patients attending a hospital rheumatology clinic, private rooms of consulting rheumatologists and a dermatology outpatient clinic were surveyed by investigator-administered questionnaire on three separate occasions. Information was sought about AUM, NSAID and selective COX-2 use and about factors likely to influence selective COX-2 prescribing. Sampling was carried out at 3, 10 and 16 months after the release of COX-2 selective inhibitors in Australia. The final survey was 3 months after Pharmaceutical Benefits Scheme (PBS) listing of celecoxib in Australia. Costs of treatment were calculated from survey findings of frequency of drug use as well as published drug prices and hospitalisation costs. RESULTS: Four-hundred and fifty-eight patients were surveyed. From the 3 months post-release to the 3 months post-PBS listing, a period of 13 months, COX-2 use in rheumatology patients increased from 18 to 57%. De novo prescription of selective COX-2 inhibitors increased from 42 to 61%. During the same period there was a fall in both NSAID (43-20%) and AUM use (41-27%). Neither selective COX-2 inhibitor nor NSAID prescription was related to risk factors for gastro-intestinal (GI) complications, but AUM use was found to correlate strongly to histories of gastroscopy, GI ulceration or GI bleed. The calculated increase in the cost of treatment was $1 033 002/10 000 patients per year. The net cost per serious GI event prevented was $71 736, compared with the normal cost of treatment of $2004. CONCLUSIONS: Among rheumatology patients, selective COX-2 inhibitors have largely replaced NSAIDs and have resulted in a reduction in AUM consumption, but prescribing patterns for selective COX-2 inhibitors have not been related clearly to risk factors for GI complications. The introduction of selective COX-2 inhibitors has been associated with a significant increase in expenditure.

Aged↗
PubMed1987

The velocity dependence of direction selectivity of visual cortical neurones in the cat.

1. The range of velocities, yielding direction-selective responses, was investigated in a total of 167 direction-selective cells from areas 17 and 18 of the cat, using a high-contrast light bar moving at velocities ranging from 0.6 to 900 deg s-1. 2. 11% of the cells were direction selective over the full range of velocities tested. Most cells (66%) gave only responses at low velocities and thus were not direction selective at high velocities. The remaining cells gave responses over a broad range of velocities but the direction selectivity was limited to either high or intermediate velocities (18 and 5% of the cells, respectively). Cells with direction selectivity at high but not at low velocities had large receptive fields with non-overlapping 'on' and 'off' subregions and they responded quickly and phasically to stationary flashes. This suggests that the latter cells relied on fast and brief interactions over large distances. 3. In thirty cells the spatial and temporal limits of direction selectivity were investigated using a stroboscopically illuminated moving light bar. In all cells direction selectivity depended both on the interflash distance and the interflash time interval. Area 17 cells with large receptive field at high eccentricity tolerated much larger interflash spacings than area 17 cells with small receptive fields near the area centralis. For eleven of the thirty cells the effective interflash distance could be larger than the width of the receptive field. The largest effective interflash time interval varied between 35 and 250 ms. 4. Eight of the thirty cells were direction selective at high but not at low velocities. These eight cells all remained direction selective over large interflash distances and they required brief interflash intervals (less than or equal to 65 ms). 5. Responses to single stroboscopic flashes within the sequence were observed in ten cells, which all responded well at high apparent velocities. While most cells (eight out of ten) showed both response increments in the preferred direction and response decrements in the non-preferred, the decrements constituted the dominant element in the direction selectivity of six out of ten cells while the remaining four cells relied mainly on response increments. 6. It is concluded that the range of direction-selective velocities of some cat visual cortical cells can be predicted from a knowledge of the spatial extent and the time course of the direction-selective interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1993

Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome.

The strategy of non-selective neuromuscular paralysis was compared with that of synchronised (fast rate) ventilation and selective paralysis in infants receiving mechanical ventilation for respiratory distress syndrome with chronic lung disease as the primary outcome measure. One hundred and ninety three infants weighing under 2000 g were randomly allocated to receive either pancuronium during mechanical ventilation in the acute phase of respiratory distress syndrome (non-selective group) or synchronised ventilation (initial ventilatory rate at or above that of the infant's) (selective group). Infants in the selective group received pancuronium if they were consistently expiring during the inspiratory phase of the ventilator cycle. There was no significant difference between the groups with respect to birth weight, gestation, and sex distribution. There was no significant difference between the group with respect to death (selective 19%, non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks' postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of ventilated infants has potential complications that may be avoided by using synchronised ventilation. As the latter is not associated with an increased incidence of long term respiratory complications, it is concluded that it is the optimum strategy of the two for ventilating infants with respiratory distress syndrome.

Chronic Disease↗