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At least 19 recordsLinked to original sources

Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting).

BACKGROUND: Temporary interruption of blood flow during carotid endarterectomy can be avoided by using a shunt across the clamped section of the carotid artery. This may improve outcome. OBJECTIVES: The objective of this review was to assess the effect of routine versus selective shunting during carotid endarterectomy, and to assess the best method for selecting patients for shunting. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Medline (1966 to 1994), Embase (1980 to 1995) and Index to Scientific and Technical Proceedings (1980 to 1994). We handsearched Annals of Surgery (1981 to 1995), British Journal of Surgery (1985 to 1995), European Journal of Vascular Surgery (1988 to 1995) and World Journal of Surgery (1978 to 1995). SELECTION CRITERIA: Randomised and quasi-randomised trials of routine shunting compared with no shunting, and trials that compared different shunting policies in patients undergoing carotid endarterectomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. The data were extracted by one reviewer and double-checked. Trial quality was assessed. MAIN RESULTS: Three trials were included. Two trials involving 590 patients compared routine shunting with no shunting. The other trial involving 131 patients compared shunting with a combination of electroencephalographic and carotid pressure measurement, with shunting by carotid pressure measurement alone. Allocation was adequately concealed in one trial, and one trial was quasi-randomised. Analysis was by intention-to-treat where possible. For routine versus no shunting, there was no significant difference in the rate of all stroke, ipsilateral stroke or death up to 30 days after surgery, although data were limited. There was no significant difference between the risk of ipsilateral stroke in patients selected for shunting with the combination of electroencephalographic and carotid pressure assessment compared to pressure assessment alone, although again the data were limited. REVIEWER'S CONCLUSIONS: The data presently available are too limited to either support or refute the use of routine or selective shunting in carotid endarterectomy. Large scale randomized trials using no shunting as the control group are required. No one method of monitoring in selective shunting has been shown to produce better outcomes.

Arteriovenous Shunt, Surgical↗

Direct responses to selection for increased litter size, decreased age at puberty, or random selection following selection for ovulation rate in swine.

Nine generations of selection for high ovulation rate were followed by two generations of random selection and then eight generations of selection for increased litter size at birth, decreased age at puberty, or continued random selection in the high ovulation rate line. A control line was maintained with random selection. Line means were regressed on generation number and on cumulative selection differentials to estimate responses to selection and realized heritabilities. Genetic parameters also were estimated by mixed-model procedures, and genetic trends were estimated with an animal model. Response to selection for ovulation rate was about 3.7 eggs. Response in litter size to selection for ovulation rate was .089 +/- .058 pigs per generation. Average differences between the high ovulation rate and control lines over generations 10 to 20 were 2.86 corpora lutea and .74 pigs (P less than .05). The regression estimate of total response to selection for litter size was 1.06 pigs per litter (P less than .01), and the realized heritability was .15 +/- .05. When the animal model was used, the estimate of response was .48 pigs per litter. Total response in litter size to selection for ovulation rate and then litter size was estimated to be 1.8 and 1.4 pigs by the two methods. Total response to selection for decreased age at puberty was estimated to be -15.7 d (P less than .01) when data were analyzed by regression (realized heritability of .25 +/- .05) and -17.1 d using the animal model. No changes in litter size occurred in the line selected for decreased age at puberty. Analyses by regression methods and mixed-model procedures gave similar estimates of responses and very similar estimates of heritabilities.

Age Factors↗

Joint effects of pleiotropic selection and stabilizing selection on the maintenance of quantitative genetic variation at mutation-selection balance.

In quantitative genetics, there are two basic "conflicting" observations: abundant polygenic variation and strong stabilizing selection that should rapidly deplete that variation. This conflict, although having attracted much theoretical attention, still stands open. Two classes of model have been proposed: real stabilizing selection directly on the metric trait under study and apparent stabilizing selection caused solely by the deleterious pleiotropic side effects of mutations on fitness. Here these models are combined and the total stabilizing selection observed is assumed to derive simultaneously through these two different mechanisms. Mutations have effects on a metric trait and on fitness, and both effects vary continuously. The genetic variance (V(G)) and the observed strength of total stabilizing selection (V(s,t)) are analyzed with a rare-alleles model. Both kinds of selection reduce V(G) but their roles in depleting it are not independent: The magnitude of pleiotropic selection depends on real stabilizing selection and such dependence is subject to the shape of the distributions of mutational effects. The genetic variation maintained thus depends on the kurtosis as well as the variance of mutational effects: All else being equal, V(G) increases with increasing leptokurtosis of mutational effects on fitness, while for a given distribution of mutational effects on fitness, V(G) decreases with increasing leptokurtosis of mutational effects on the trait. The V(G) and V(s,t) are determined primarily by real stabilizing selection while pleiotropic effects, which can be large, have only a limited impact. This finding provides some promise that a high heritability can be explained under strong total stabilizing selection for what are regarded as typical values of mutation and selection parameters.

Genetic Variation↗

Factors that influence prescribers in their selection and use of COX-2 selective inhibitors as opposed to non-selective NSAIDs.

OBJECTIVE: To identify factors that influence prescribers in their selection and use of cyclo-oxygenase-2 (COX-2) selective inhibitors as opposed to non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and report the tendency to co-prescribe gastro-protection with these agents. SETTING: All 579 general practitioners (GPs) in one geographical area, Lothian, Scotland, UK. METHOD: Postal questionnaires; simple and factorial designed case series questionnaire. MAIN OUTCOME MEASURES: Categorisation of responses to clinical and non-clinical factors into highly, partially or not influential. The quantitative influence of the most prominent clinical factors on prescribing choice and the tendency of co-prescription of gastro-protection with these agents. RESULTS: Responses from 229 (40%) GPs suggested the following as most influential: Drug Evaluation Panel recommendations, Lothian Joint Formulary, local practice formulary, history of peptic ulcer disease (PUD), history of gastro-intestinal (GI) adverse effects with NSAIDs and advanced age. Advice from other physicians, patient demand, history of alcohol gastritis, history of gastro-oesophageal reflux disease, history of functional dyspepsia, concomitant use of low dose aspirin and concomitant use of gastro-protective agents were regarded to have moderate influence. Information directly from pharmaceutical industry and regular smoking were regarded as having weak influence. An 18% response to the factorial designed questionnaire using the most prominent clinical factors suggested that history of either GI adverse effects associated with non-selective NSAIDs or PUD resulted in more pronounced increase in the frequency (15%) of decision to prescribe COX-2 selective inhibitors than advanced age (10%). Concomitant use of low dose aspirin had little effect on GPs' decisions. The mean percentage of GPs choosing to co-prescribe gastro-protection was higher with non-selective NSAIDs (64%) than with COX-2 selective inhibitors (22%). CONCLUSION: Local authoritative guidance and history of GI complications highly influenced the GPs in their use and choice of either COX-2 selective inhibitors or non-selective NSAIDs. As expected the use of gastro-protection was more frequently chosen with non-selective NSAIDs than COX-2 selective inhibitors.

Age Factors↗

K-selection, alpha-selection, effectiveness, and tolerance in competition: density-dependent selection revisited.

In the Drosophila literature, selection for faster development and selection for adapting to high density are often confounded, leading, for example, to the expectation that selection for faster development should also lead to higher competitive ability. At the same time, results from experimental studies on evolution at high density do not agree with many of the predictions from classical density-dependent selection theory. We put together a number of theoretical and empirical results from the literature, and some new experimental results on Drosophila populations successfully subjected to selection for faster development, to argue for a broader interpretation of density-dependent selection. We show that incorporating notions of alpha-selection, and the division of competitive ability into effectiveness and tolerance components, into the concept of density-dependent selection yields a formulation that allows for a better understanding of the empirical results. We also use this broader formulation to predict that selection for faster development in Drosophila should, in fact, lead to the correlated evolution of decreased competitive ability, even though it does lead to the evolution of greater efficiency and higher population growth rates at high density when in monotypic culture.

Animals↗

Sexual selection favors female-biased sex ratios: the balance between the opposing forces of sex-ratio selection and sexual selection.

In a verbal model, Trivers and Willard proposed that, whenever there is sexual selection among males, natural selection should favor mothers that produce sons when in good condition but daughters when in poor condition. The predictions of this model have been the subject of recent debate. We present an explicit population genetic model for the evolution of a maternal-effect gene that biases offspring sex ratio. We show that, like local mate competition, sexual selection favors female-biased sex ratios whenever maternal condition affects the reproductive competitive ability of sons. However, Fisherian sex-ratio selection, which favors a balanced sex ratio, is an opposing force. We show that the evolution of maternal sex-ratio biasing by these opposing selection forces requires a positive covariance across environments between the sex-ratio bias toward sons (b) and the mating success of sons (r). This covariance alone is not a sufficient condition for the evolution of maternal sex-ratio biasing; it must be sufficiently positive to outweigh the opposing sex-ratio selection. To identify the necessary and sufficient conditions, we partition total evolutionary change into three components: (1) maternal sex-ratio bias, (2) sexual selection on sons, and (3) sex-ratio selection. Because the magnitude of the first component asymmetrically affects the strength of the second, biasing broods toward females in a poor environment evolves faster than the same degree of bias toward males in a good environment. Consequently, female-biased sex ratios, rather than male-biased sex ratios, are more likely to evolve. We discuss our findings in the context of the primary sex-ratio biases observed in strongly sexually selected species and indicate how this perspective can assist the experimental study of sex ratio evolution.

Alleles↗

"Selective" switching from non-selective to selective non-steroidal anti-inflammatory drugs.

BACKGROUND: Non-steroidal anti inflammatory drugs (NSAIDs) are thought to account for almost 25% of all reported adverse drug reactions, primarily gastrointestinal (GI) toxicity. Selective cyclo-oxygenase-2 (COX-2) inhibitors have been shown to preferentially inhibit activity of the COX-2 enzyme, which maintains anti-inflammatory activity but reduces GI toxicity. OBJECTIVE: To determine the degree of switching from non-selective NSAIDs to COX-2 inhibitors and to examine the factors that were associated with switching. METHODS: The General Medical Services prescription database (1.2 million people) was examined for NSAID prescriptions from December 1999 through November 2001. All those receiving non-selective NSAIDs and those switching to selective COX-2 inhibitors after at least 1 month on a non-selective NSAID were identified (non-switchers and switchers, respectively). Age, sex, dose of non-selective NSAID and co-prescribing of anti-peptic ulcer (anti-PU) drugs were considered between switchers and non-switchers, and odds ratios (OR) calculated using logistic regression. The effect of chronic use (> or =3 months prescription of a non-selective NSAID during the study period) on switching was also evaluated. RESULTS: A total of 81,538 of 480,573 patients (17%) initially prescribed non-selective NSAIDs were switched to COX-2 inhibitors during the study. The elderly (65 years or older) were more likely to be switched to a COX-2 inhibitor [OR=1.81, 95% confidence interval (CI) 1.79, 1.84]. Women were also more likely to be switched to COX-2 inhibitor therapy (OR=1.25, 95% CI 1.23, 1.27). Previous but not subsequent prescribing of anti-PU drugs was also associated with switching. Chronic users showed similar switching patterns. CONCLUSIONS: Prescribers are more likely to switch older female patients and those with a past history of peptic ulcers from non-selective NSAIDs to COX-2 inhibitors. This suggests that doctors take risk factors into consideration when prescribing NSAIDs. The relatively low rate of switching may suggest that prescribers still have concerns over the place of COX-2 inhibitors and reserve their use to those patients particularly at risk of NSAID-induced GI toxicity.

Age Factors↗

T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.

Animals↗

Self-selection of standards by children: The relative effectiveness of pupil-selected and teacher-selected standards of performance.

This study examines the effects of contingent reinforcement under conditions of pupil-selected and teacher-selected performance standards upon pupils' academic response rates. The academic response rate was measured by the number of correct responses emitted per session. Thirty pupils (15 second-graders and 15 third-graders) were randomly assigned to one of three experimental groups, based on matched triplets. One group worked under pupil-selected standards; the second group worked under standards selected by the experimenter with each pupil yoked to a member of the pupil-selected standards groups. Both groups participated in the calculation of their daily earnings. The third group served as a no-contingency control group. Baseline academic response rates on writing and math tasks were determined. During the experimental sessions reinforcement was provided in the form of points which were later traded for tangible rewards. The pupil-selected standards group showed a significantly greater number of correct responses in the writing and math tasks than the externally selected standards group.

Journal Article↗

Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. The iterative inhibitor design and evaluation with assistance of the selectivity screen served to differentiate otherwise indistinguishable inhibitors permitting the simultaneous optimization of potency and selectivity. Significantly, the simultaneous assessment of all potential competitive enzymes with the selectivity screen does not require the use of expressed or purified enzymes or a competitive substrate, no modification of the inhibitors is required, and the relative potency for competitive enzymes can be quantified (IC50's) including those that lack known substrates or function.

Amidohydrolases↗

Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor.

Observation that the G protein-coupled P2U receptor (P2Y2 receptor) is activated by UTP as well as ATP provided the first indication that a class of uridine nucleotide-responsive receptors might exist. This hypothesis was confirmed by our identification of a uridine nucleotide-specific receptor on C6-2B rat glioma cells and by the recent cloning of two uridine nucleotide-responsive receptors, the P2Y6 receptor [J. Biol. Chem. 270:26152-26158 (1995)] and the P2Y4 receptor [J. Biol. Chem. 270:30849-30852 (1995) and J. Biol. Chem. 270:30845-30848 (1995)]. The relative nucleotide selectivities of these uridine nucleotide-activated receptors have not been established. Therefore, we cloned and expressed the P2Y6 and P2Y4 receptors in 1321N1 human astrocytoma cells and compared their relative selectivities for UDP, UTP, and other uridine and adenine nucleotides with that of the P2Y2 receptor expressed in the same cells. These comparisons were made by measuring inositol phosphate accumulation under conditions in which the initial purity and stability of agonists were rigidly ensured and quantitatively assessed. The data indicate that the P2Y2 receptor is activated with similar potencies by ATP and UTP but not by ADP or UDP; the P2Y6 receptor is activated most potently by UDP but weakly by UTP, ATP, and ADP; and the P2Y4 receptor is activated most potently by UTP, less potently by ATP, and not at all by nucleotide diphosphates. Furthermore, the P2Y6 receptor, which displays a uridine nucleotide selectivity essentially identical to that of the uridine nucleotide-specific receptor in C6-2B cells, was shown to be natively expressed in C6-2B cells and to account for the uridine nucleotide responses originally identified in these cells. These results define the uridine nucleotide selectivity of three phospholipase C-linked receptors: a receptor that is selectively activated by UDP (P2Y6 receptor), selectively activated by UTP (P2Y4 receptor), and activated by UTP and ATP but not by diphosphate nucleotides (P2Y2 receptor).

Adenosine Triphosphate↗

Influence of the affinity of selecting ligands on T cell positive and negative selection and the functional maturity of the positively selected T cells.

Interaction of the TCR on immature thymocytes with ligands on antigen presenting cells can lead to different fates including positive and negative selection. The affinity of the selecting ligands plays an important role in determining these outcomes. We used the 2C TCR transgenic model to evaluate the efficacy of ligands with widely differing affinity (3 x 10(3) - 2 x 10(6) M-1) for the 2C TCR in mediating thymic negative and positive selection. Our results support the conclusions that the deletion of immature thymocytes is not only mediated by high-affinity ligands but also by low-affinity/avidity ligands. However, high- and low-affinity ligands differ in their requirements for negative selection. We also present evidence that positive selection is not an all or none process but depending on the strength of interaction between the ligand and the TCR during the positive selection process can result in single positive thymocytes that are at different stages of functional maturity.

Animals↗

Natural selection associated with birth weight. I. Selection intensity and selective deaths from birth to one month of life.

Differential mortality as a function of birth weight was studied up to the 4th week of life in all single births in Italy in 1974. It was found that: (i) Both selection intensity and selective mortality are much higher with increasing immaturity. (ii) For babies born at term or after 8 months of pregnancy selection intensity tends to relax as early as one week after birth, while for those born after 7 months selection is at work for a longer period. (iii) Selective mortality, on the other hand, keeps increasing after birth but its relevance is relatively decreasing since average mortality after birth continues to decrease.

Birth Weight↗

Kinetic parameters of antagonism by the delta opioid receptor selective peptide antagonist Boc-Tyr-Pro-Gly-Phe-Leu-Thr against selective and non-selective agonists in the mouse vas deferens.

The kinetic parameters of antagonism by the delta opioid receptor selective antagonist N-t-Boc-Tyr-Pro-Gly-Phe-Leu-Thr, obtained by using moderately selective or selective agonists, were compared in the mouse vas deferens bioassay. The apparent affinity for the preferred receptor type was 6.8 times higher when selective agonist was used, resulting in a Ke of 81.4 nM (66.3-99.9, n = 6) against [D-Ala2, D-Leu5]-enkephalin, with a 3700-fold delta over mu or kappa selectivity ratio.

Analgesics↗

An unambiguous assignment method by 2D selective-TOCSY-HSQC and selective-TOCSY-DQFCOSY and structural analysis by selective-TOCSY-NOESY experiments of a biantennary undecasaccharide.

In this paper we present a newly developed 2D selective-TOCSY-HSQC experiment for unambiguous assignment of individual sugar components of a biantennary undecasaccharide. The correlation signals between the protons and carbons of a selectively excited sugar component in the undecasaccharide were observed in a 2D selective-TOCSY-HSQC experiment. The network of proton signals of this sugar was observed in a 2D selective-TOCSY-DQFCOSY experiment. These two experiments enabled us to perform unambiguous sequential assignment of both protons and carbons of the individual sugar components in the undecasaccharide. In addition, a three-dimensional structural analysis was performed by a 2D selective-TOCSY-NOESY experiment, which clearly distinguishes between inter-sugar and intra-sugar ring NOE signals.

Carbohydrate Conformation↗

Genetic Algorithm guided Selection: variable selection and subset selection.

A novel Genetic Algorithm guided Selection method, GAS, has been described. The method utilizes a simple encoding scheme which can represent both compounds and variables used to construct a QSAR/QSPR model. A genetic algorithm is then utilized to simultaneously optimize the encoded variables that include both descriptors and compound subsets. The GAS method generates multiple models each applying to a subset of the compounds. Typically the subsets represent clusters with different chemotypes. Also a procedure based on molecular similarity is presented to determine which model should be applied to a given test set compound. The variable selection method implemented in GAS has been tested and compared using the Selwood data set (n = 31 compounds; v = 53 descriptors). The results showed that the method is comparable to other published methods. The subset selection method implemented in GAS has been first tested using an artificial data set (n = 100 points; v = 1 descriptor) to examine its ability to subset data points and second applied to analyze the XLOGP data set (n = 1831 compounds; v = 126 descriptors). The method is able to correctly identify artificial data points belonging to various subsets. The analysis of the XLOGP data set shows that the subset selection method can be useful in improving a QSAR/QSPR model when the variable selection method fails.

Algorithms↗

Faking and selection: considering the use of personality from select-in and select-out perspectives.

The effects of faking on criterion-related validity and the quality of selection decisions are examined in the present study by combining the control of an experiment with the realism of an applicant setting. Participants completed an achievement motivation measure in either a control group or an incentive group and then completed a performance task. With respect to validity, greater prediction error was found in the incentive condition among those with scores at the high end of the predictor distribution. When selection ratios were small, those in the incentive condition were more likely to be selected and had lower mean performance than those in the control group. Implications for using personality assessments from select-in and select-out strategies are discussed.

Achievement↗

The effects of non-selective, preferential-selective and selective COX-inhibitors on the growth of experimental and human tumors in mice related to prostanoid receptors.

Earlier observations on cyclo-oxygenase inhibitors (NSAIDs) restricting tumor growth were re-evaluated by comparing the effects of non-selective, preferential selective and selective derivatives of COX-inhibitors on tumor growth in mouse models with either prostaglandin-sensitive (MCG-101, human tumors) and -insensitive transplants (K1735-M2). Tumor growth, with and without provision of a classical cyclo-oxygenase inhibitor (indomethacin), was related to tumor content of COX-1/COX-2 protein as well as to EP1-EP4 and prostacyclin receptor expression. Mouse serum amyloid protein (SAP) was measured as an indicator of systemic inflammation, which relates to pro-inflammatory cytokines. Indomethacin inhibited tumor growth and prolonged the survival of mice bearing MCG-101 tumors, which display a high production of PGE2, while K1735-M2 tumors with insignificant amounts of PGE2 did not respond to indomethacin at all. However, the effects of various NSAIDs on tumor growth were highly variable in combination with the fact that most preferential selective and selective COX-2 inhibitors attenuated poorly systemic inflammation evaluated by plasma concentrations of mouse SAP. The ability of NSAIDs to attenuate tumor growth was not related to the tumor content of COX-2 protein as expected. Multivariate analysis suggests that significant COX-inhibition of tumor growth may be related to tumor expression of subtype EP2, EP3 (p<0.005) and perhaps EP4 (p<0.09) in complex interplay. The extent of tumor growth inhibition by COX-inhibitors is not simply related to drug specificity on COX-1 or COX-2 pathways. Such effects may instead be related to tumor expression of prostanoid receptors in tumor tissue.

Amyloid↗