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Short-term studies underestimate 30-generation changes in a butterfly metapopulation.

Most studies of rare and endangered species are based on work carried out within one generation, or over one to a few generations of the study organism. We report the results of a study that spans 30 generations (years) of the entire natural range of a butterfly race that is endemic to 35 km(2) of north Wales, UK. Short-term studies (surveys in single years and dynamics over 4 years) of this system led to the prediction that the regional distribution would be quite stable, and that colonization and extinction dynamics would be relatively unimportant. However, a longer-term study revealed unexpectedly high levels of population turnover (local extinction and colonization), affecting 18 out of the 20 patches that were occupied at any time during the period. Modelling the system (using the 'incidence function model' (IFM) for metapopulations) also showed higher levels of colonization and extinction with increasing duration of the study. The longer-term dynamics observed in this system can be compared, at a metapopulation level, with the increased levels of variation observed with increasing time that have been observed in single populations. Long-term changes may arise from local changes in the environment that make individual patches more or less suitable for the butterfly, or from unusual colonization or extinction events that take metapopulations into alternative states. One implication is that metapopulation and population viability analyses based on studies that cover only a few animal or plant generations may underestimate extinction threats.

Animals↗

Proxies for healthcare need among populations: validation of alternatives--a study in Quebec.

STUDY OBJECTIVE: To compare the use of a non-mortality based proxy for relative needs for healthcare among regional populations with a mortality based proxy for population relative needs and to evaluate the additional value of a proxy based on a combination of non-mortality and mortality based proxies. DESIGN: Analysis of cross sectional data on mortality, socioeconomic status, and self assessments of health taken from registrar general records, a population census, and a population health survey. SETTING: The province of Quebec, Canada. COVERAGE: The populations of the 15 health regions in Quebec. MAIN OUTCOME MEASURE: The levels of correlation of indicators based on mortality data, socioeconomic data, and combined data with a standardised indicator of self assessed health. RESULTS: Variations in scores of a proxy based on socioeconomic data among regions explain 37% of the observed variation in self assessed health, 4% more than the level of variation explained by the standardised mortality rate scores. A weighted combination of both mortality and socioeconomic based proxies explains 56% of variation in self assessed health. CONCLUSIONS: Justification of "deprivation weights" reflecting variations in socioeconomic status among populations should be based on empirical support concerning the performance of such weights as proxies for relative levels of need among populations. The socioeconomic proxy developed in this study provides a closer correlation to the self assessed health of the populations under study than the mortality based proxy. The superior performance of the combined indicator suggests that the development of social deprivation indicators should be viewed as a complement to, as opposed to a substitute for, mortality based measures in needs based resource allocation exercises.

Adolescent↗

Detection of quantitative trait loci affecting caffeine metabolism by interval mapping in a genome-wide scan of C3H/HeJ x APN F(2) mice.

Caffeine metabolite ratios have been widely used to measure cytochrome P-450 1A2 activity in humans. Serum paraxanthine/caffeine ratio is one such index of this activity. We had previously demonstrated genetic variation of this trait among inbred mouse strains. In the present study, we have undertaken a genome-wide scan for quantitative trait loci affecting this trait with an interval mapping approach on an F(2) intercross population of acetaminophen nonsusceptible and C3H/HeJ inbred mice. A statistically significant association (log-likelihood ratio = 25.0) between a locus on chromosome 9, which colocalized with the murine Cyp1a2 locus, and the plasma paraxanthine/caffeine ratio was identified. This result suggested the presence of an expression polymorphism affecting this gene. A second locus was identified on chromosome 1 (log-likelihood ratio = 9.7) for which no obvious candidate gene has been identified. The influence of this locus on the paraxanthine/caffeine index was more significant among males (log-likelihood ratio = 6.3) than females (log-likelihood ratio = 3.6). A third locus was identified on chromosome 4 with a less statistically robust association (log-likelihood ratio = 3.4) to the paraxanthine/caffeine phenotype. Collectively, these three loci accounted for 63.2% of the variation observed in the F(2) population for this phenotype. These results demonstrate the potential for genetic variation arising from factors other than CYP1A2 activity to influence the plasma paraxanthine/caffeine ratio in mice. This study demonstrates the utility of quantitative genetics in the analysis of polygenic drug metabolism.

Animals↗

Anatomic variations in patients operated for bladder substitution.

Authors review the anatomic variations observed throughout orthotopic ileal neobladder formation in 38 cases following radical cystectomy. A part of the variations was necessitated because of deviation from the classic Hautmann-type surgical technique: in 6 cases the site of ileal resection was modified due to abnormal mesenterial art. course, on 2 occasions Meckel diverticules were detected while cutting the ileal neobladder, in 13 cases the laterally adhered sigma bladder necessitated the left-sided ureter to be pulled through beneath the mesosigma for the purpose of making sure the ureter--ileal neobladder anastomosis became free of any tension, while on 1 occasion the left ureteral preparations went with some injury. Since the left ureter became short, ureter replacement variation was needed, similar to the Studer method of ileal neobladder formation. All these variations, however, did not implicate the essence of the Hautmann technique. Follow-up of the patients did not reveal high frequency of occurrence of any complications.

Aged↗

Evidence implicating MHC genes in the immunological nonresponsiveness to the Plasmodium falciparum CS protein.

The circumsporozoite (CS) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. Both cytotoxic T cells (CTL) and antibody specific for the CS protein are thought to be important in protection. By examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (MHC) are important for immune responsiveness. F1 mice between high antibody responders and low antibody responders are high antibody responders, suggesting that in this model immune suppressor genes do not control the immune response. Using synthetic peptides to map epitopes for CTL and helper T cells (which are important for the antibody response) we have shown that the T-cell epitopes are located in the polymorphic region of the protein, and we hypothesize that T cells have indeed selected the variation observed in the CS protein. The success of subunit vaccines will depend on the pattern of variation in different geographical locations, the ability to construct multivalent vaccines containing different variant epitopes from this protein, and on the existence of other sporozoite and liver-stage proteins involved in protection.

Animals↗

The evaluation of morphological characteristics of human spermatozoa according to stricter criteria.

The evaluation of the morphology of human spermatozoa varies widely between and sometimes even within laboratories. The purpose of this study was to determine whether the method that has been developed in our laboratory and which resulted in the use of stricter criteria for the evaluation of sperm morphology is a practical, reliable and repeatable method and to establish the within and between observer variations. The criteria used for a 'normal' spermatozoon are based on the appearance of spermatozoa found in the mucus of the upper endocervical canal. The results of the morphological evaluations of 26 samples by four observers were statistically analysed by various methods. The method of Barnett showed a high degree of relative accuracy between observers with error variances of between 2.89 and 19.67 as well as high Spearman rank correlation coefficients of between 0.8675 and 0.6537 (P less than 0.0003). The Spearman correlation coefficient for 15 duplicate evaluations by one observer was 0.9650 (P less than 0.0001) while the coefficients of variation for repeated evaluations of single samples were also within acceptable limits. Based on these results, the method described in this article allows comparable and reliable results between and within observers to be obtained. From this and other studies it can be concluded that the method also has a good prognostic value for the prediction of expected IVF fertilization, the hamster test and hemizona assay.

Cytodiagnosis↗

[Acute bone and joint infections in children: how much attention should be paid to persistent fever during intravenous antibiotic therapy?].

PURPOSE OF THE STUDY: Bone and joint infections are challenging therapeutic situations requiring rapid antibiotic therapy as soon as bacteriology specimens have been obtained. Laboratory tests (C reactive protein, erythrocyte sedimentation rate, white cell count) and clinical findings are used to assess therapeutic efficacy. Most of the clinical signs however, particularly in children or after a surgical procedure, are not explicit enough to allow proper assessment of the clinical course under antibiotic therapy. Body temperature is the only parameter currently used in routine practice. But the measurement of body temperature is not always reliable and variations observed during treatment should not always be attributed to treatment failure. The purpose of this work was to assess the significance of changes in body temperature observed in children given effective intravenous antibiotic treatment for bone and joint infections. MATERIAL AND METHODS: We reviewed retrospectively the files of 60 children treated in our unit for acute bone and joint infections. The patients had acute hematogeneous osteomyelitis (n=27), septic arthritis (n=25), and infectious osteoarthritis (n=8). A bacterial strain was identified on cultures of blood, joint fluid, or metaphysis puncture samples in all cases. Blood test results (C-reactive protein, erythrocyte sedimentation rate, white cell count) were recorded during treatment. Body temperature was recorded three times a day until normalization then daily until discharge. We searched for correlations between variations in the temperature curve observed during treatment and blood test results. RESULTS: Ninety percent of the children had fever at admission (mean 39.1 degrees C). Among the six children without fever, the temperature rose in 5 during the first 48 hours of hospitalization. Even when the treatment was effective, apyrexia was achieved slowly, on the average after 8 days of antibiotic treatment. We also observed that the peak temperature occurred during the first 5 days of antibiotic treatment considered effective. C-reactive protein level normalized within a satisfactory time (10.5 days), reflecting the efficacy of the antibiotics. DISCUSSION: The efficacy of antibiotic treatment must always be verified in patients with acute bone and joint infections. Generally, biological parameters are used to monitor efficacy. Currently, C-reactive protein appears to be the most reliable parameter to assess efficacy, its rapid decline reflecting clinical cure. Erythrocyte sedimentation rate and white cell counts are poor surveillance parameters. Finally, body temperature is not a specific surveillance parameter and persistent fever during treatment does not necessarily signify ineffective antibiotic treatment. In light of this fact, body temperature should always be compared with C-reactive protein level to draw any conclusion concerning therapeutic failure.

Adolescent↗

A simulation test of hominoid species number at Lufeng, China: implications for the use of the coefficient of variation in paleotaxonomy.

High dental metric variation in the large hominoid sample from the late Miocene site of Lufeng, China has been interpreted in two ways: (1) there are two morphologically similar species that broadly overlap in size, and (2) there is one species that is more highly sexually dimorphic in dental size, and perhaps in body size, than any extant primate. It has been claimed that the high levels of dental metric variation falsify the single-species hypothesis, which has been viewed implicitly as corroboration of the two-species hypothesis. However, the two-species hypothesis has not been subjected to testing. Here we test the two-species hypothesis using computer simulations to attempt to reproduce the unusual pattern of intrasexual and intersexual dental metric variation observed in the Lufeng postcanine dentition. Conditions of the simulation experiments were optimized to favor the two-species hypothesis. It was found that, although the Lufeng pattern of metric variation could be reproduced by sampling two species, the likelihood of this occurrence was very low even when the conditions were optimized to the point of improbability. We conclude that the likelihood is very high that the Lufeng sample is composed of one species that is more highly sexually dimorphic in the postcanine dentition than any extent primate species. If so, then the high levels of sexual dimorphism and intraspecific dental metric variation in this species violate the central assumption of methods that employ the coefficient of variation (CV) for paleotaxonomy, namely, that neither can lie outside the ranges observed among extant species. Thus, we further conclude that the CV must be used with caution when evaluating the taxonomic composition of fossil samples and, further, that it cannot be used to falsify a single-species hypothesis in any meaningful way. Other fossil hominoid samples with high measures of dental variation may indicate that considerable sexual size dimorphism typified many Eurasian middle-late Miocene hominoids.

Animals↗

Molar morphology and variation in two malagasy lemur families (Lemuridae and Indriidae).

The lemurs of Madagascar represent a radiation of primates exhibiting considerable ecological and morphological diversity. Dentally, all lemurs possess the characteristic strepsirhine anterior tooth comb, but exhibit variation in their postcanine teeth that may be related to dietary differences. In this study, I examine two factors that could complicate a strictly functional interpretation of tooth form variation in two families of Malagasy primates, the Lemuridae and Indriidae. (1) Allometry may be responsible for observed variation. Body size, not specific tooth features, may be the object of selection; tooth features may vary among taxa as a consequence of differences in body size. (2) Taxonomic affiliation may "explain" variation without recourse to functional explanations. Tooth morphology among closely-related taxa may be constrained developmentally or as a result of stabilizing selection. Morphological variation between families, therefore, may not be the result of current functional differences related to physical dietary properties, but may result from past events that are lineage-specific. Morphological features from the upper and lower second molars of seven lemurid and four indriid taxa are compared. The results of this study indicate that the majority of second molar features scale isometrically. Initial separation by families is warranted by the homogeneous slopes but different elevations in analyses of covariance between families. Intrafamilial variation is considerable for lemurids, but more discrete among indriids. Functional explanations for tooth form variability should take into consideration the degree of variation within taxa. For this particular dataset, the two families should be analyzed separately, and, because of the considerable overlap of subspecies with full species among lemurids, the lowest taxonomic unit recognized should be used.

Analysis of Variance↗

Exchanges of short polymorphic DNA segments predating speciation in feline major histocompatibility complex class I genes.

Sequence comparisons of 14 distinct MHC class I cDNA clones isolated from species representing the three major taxonomic lineages of Felidae (domestic cat lineage, ocelot lineage, and pantherine lineage) revealed that feline MHC class I alleles have highly mosaic structures with short polymorphic sequence motifs that are rearranged between alleles of individual MHC loci, between MHC class I genes within cat species, and between homologous MHC loci in different species. The pattern of sequence variation in felids supports the role of the following factors in production and maintenance of MHC variation: (1) gradual spontaneous mutation; (2) selective pressure to conserve certain residues but also to vary in hypervariable regions, notably residues that functionally participate in antigen recognition and presentation; and (3) recombination-mediated gene exchange between alleles and between related genes. The overall amount of genetic variation observed among MHC class I genes in the Felidae family is no greater than the amount of variation within any outbred cat species (i.e., domestic cat, ocelot). The occurrence of equivalent levels of polymorphism plus the simultaneous persistence of the same sequence motifs in divergent feline species suggest that most MHC class I nucleotide site polymorphism predated species divergences. Ancient polymorphisms have been transmitted through the speciation events and modern feline MHC class I alleles were derived by recombinational exchange of polymorphic sequence motifs. Moreover, some of these sequence motifs were found in other mammalian MHC class I genes, such as classical human HLA-B5, nonclassical human HLA-E class I genes, and bovine class I genes. These results raise the prospect of an ancient origin for some motifs, although the possibility of convergence in parallel mammalian radiations cannot be excluded.

Amino Acid Sequence↗

Circadian effect on carbamazepine kinetics in rat.

The purpose of the present study was to investigate whether the time of day (24 h) at which carbamazepine is administered influences its pharmacokinetics in the rat. The pharmacokinetics of a single, 100 mg . kg-1 bodyweight per os, dose of carbamazepine were studied at four different fixed time points of a 24-hour period (i.e. 10.00, 16.00, 22.00 or 04.00 h) in Wistar AF-SPF adult male rats maintained under controlled environmental conditions (LD: 18.00 - 06.00h) during October 1978. The total plasma levels and the unbound fraction were measured according to an immunoenzymatic method (EMIT). The effects of fasting were also investigated. The data shows circadian variations of pharmacokinetic parameters: the maximum peak concentration and the maximum time to reach this peak was observed when the drug was given respectively at 16.00h and at 10.00h. The elimination half-life varied from 15.15 hours at 16.00h to 10.48 hours at 22.00h. The observed variations may be related to: daily fluctuations of absorption or binding of the drug; diurnal variations of the hepatic drug metabolizing enzymes responsible for the inactivation; and/or diurnal variations in excretion rate of the drug.

Administration, Oral↗

Biosynthesis and inactivation of ecdysone during the pupal-adult development of the cabbage butterfly, Pieris brassicae L.

Injection of labelled ecdysone and 2-hydroxyecdysone into Pieris pupae showed that their catabolism proceeds through 26-hydroxylation followed by conversion into acidic steroids assumed to be 26-oic compounds. This biological system is characterized by the lack of conjugation reactions and by rather long-lived hormones. In vivo biosynthesis of ecdysteroids was investigated by 24 hr [3H]cholesterol labelling, followed by HPLC analysis of the resulting [3H]ecdysone and 20-hydroxyecdysone. Active conversion (up to 0.07% in 24 hours) was observed between 48 hr and 120 hr following pupal ecdysis, a result in good agreement with the variations observed in hormone content. Long-term [3H]cholesterol incorporation experiments made it possible to monitor ecdysteroid dynamics during pupal development. Three periods were observed, corresponding to successive accumulation of ecdysone, 20-hydroxyecdysone and an acidic metabolite. Comparison of these results with those of the experiments involving labelled ecdysone injection shows that the catabolism of injected hormones is not the same as that of endogenous hormones.

Animals↗

Tracing the sources of cellular variation.

As the adage says, variety is the spice of life, and despite our best attempts, cells, even those with the same genome, never seem to behave the same. By combining mathematical and experimental analyses, Colman-Lerner and colleagues propose, in a recent issue of Nature, a method to delicately unravel the sources of this variation. Applying their technique to the pheromone response in budding yeast, they show that much of the observed variation originates from cell cycle effects and is dependent on levels of pathway input.

Cell Cycle↗

Consistency of patient- and doctor-assessed cosmetic outcome after conservative treatment of breast cancer.

The cosmetic results of the breast (144 patients) were analysed after segmental resection and axillary dissection with or without postoperative radiotherapy for early low-risk breast cancers. Cosmetic results were assessed over time (3, 9, 18, 36, 48 months respectively) by the patient and by the physician. Patients rated the overall cosmetic result good or excellent in 92% of cases after 3 months. The proportion of good or excellent cosmetic results decreased over time and after four years 89% of patients classified themselves in this category, whereas the physician assessed the outcome as good or excellent in 91% of cases after 3 months and 75% after 4 years. The inter-observer consistency between physician and patient in assessing the cosmetic outcome was kappa = 0.42 at the beginning and decreased over time (kappa = 0.07 after 4 years). The intra-observer variation over time was kappa = 0.53 for the patient and kappa = 0.32 for the physician. Inter-observer consistency between patient and physician was moderate immediately following treatment but decreased over time. The feeling of satisfaction of the patient was relatively stable whereas the opinion of the physician became somewhat more critical over time. Therefore the intra-observer consistency over time was somewhat better for the patient than for the physician.

Breast Neoplasms↗

Analyzing geographic patterns of disease incidence: rates of late-stage colorectal cancer in Iowa.

This study, using geocodes of the locations of residence of newly diagnosed colorectal cancer patients from the Iowa Cancer Registry, computed continuous spatial patterns of late-stage rates of colorectal cancer in Iowa. Variations in rates in intrahospital service regions were as great as interhospital service regions, shown by analysis of variance tests. Some of the spatial variations observed could be explained, using a general linear regression model on individual-level data, by spatial variations in attributes of individuals and their relationships to health resources. We show how this source of variation can be removed from the original map leaving a new map showing the remaining variation in late-stage rate not explained by these relationships. We argue that it would be more appropriate to organize prevention and control activities targeted at the areas with higher than expected late-stage rates shown on this map. The originality of this approach is in the integration of geocoded data from a cancer registry with methods of spatial analysis that provide considerable geographic detail in the cancer rate while controlling for rate stabilization and reliability due to the small number problem.

Colorectal Neoplasms↗

A multi-centre evaluation of the intra-assay and inter-assay variation of commercial and in-house anti-cardiolipin antibody assays.

AIMS: To assess the intra-assay (intra-run) and inter-assay (inter-run) variation of commercial and in-house IgG and IgM anti-cardiolipin antibody (aCL) assays/kits, and to determine an appropriate maximum value for inclusion in consensus guidelines. METHODS: Frozen aliquots of two patient specimens and one commercial control were sent to nine laboratories for the evaluation of eight commercial kits and one in-house assay. Intra-assay and inter-assay evaluations were performed with all three samples for IgG aCL, and one patient specimen for IgM aCL. RESULTS: The IgG and IgM aCL values varied considerably between the nine assays/kits. The majority of assays/kits demonstrated less than 20% intra-assay and inter-assay variation, with lower intra-assay and inter-assay variation observed with the commercial control. Single calibrator assays were not consistently associated with higher inter-assay variation than multi-point calibrator assays. CONCLUSIONS: An inter-assay coefficient of variation of 20% was determined to be an appropriate maximum value for inclusion in the Australasian aCL Working Party consensus guidelines. Improved standardisation between different assay/kits is still required.

Antibodies, Anticardiolipin↗

Identification of important functional environs in protein tertiary structures from the analysis of residue variation in 3-D: application to cytochromes c and carboxypeptidases A and B.

A simple methodology is described to apply to aligned protein sequence sets for which at least one representative 3-D C alpha structure is known. The evolutionary variation observed at each residue position in the sequence alignment is qualified by taking into account the residue variation that has occurred at other positions located within 7 A (according to the probable chain fold). This expresses the evolutionary behaviour of any residue position in the more appropriate context of its immediate surroundings and distinguishes between invariant residues on the basis of the variation of their environment. The highest mechanistic significance is attached to conserved residues in conserved surroundings, but the quantitative nature of the analysis means that all residue vicinities can be ranked and merged according to the degree of conservation that they exhibit and the residue positions that comprise them. Therefore, with the aid of the chain fold, contour maps can be constructed that show graded foci of evolutionary conservation in the underlying superstructure of the protein type, and the irregular shapes and extents of large conserved areas. To test the methodology, it was applied to cytochromes c and the carboxypeptidases A and B.

Biological Evolution↗

Natural selection on age-specific fertilities in human females: comparison of individual-level fitness measures.

Lifetime reproductive success and timing of reproduction are key components of life-history evolution. To understand the evolution of reproductive schedules, it is important to use a measure of fitness that is sensitive both to reproductive quantity and reproductive timing. There is a contradiction between the theory, which mainly focuses on the rate measures of fitness (r and lambda), and empirical studies, which mainly use lifetime reproductive success (LRS), or some of its correlates, as a fitness measure. We measured phenotypic selection on age-specific fertilities in three pre-modern human populations using individually estimated finite rate of increase, er (lambda). We found that lambda and lifetime reproductive success ranked individuals differently according to their fitness: for example, a female giving birth to four children at a young age may actually have a higher fitness than a female giving birth to six children at a greater age. Increase in fertility at the young age classes (15-19 years) was favoured by selection, but the intensity of selection on fertility was higher in the older age classes (20-30 years), where the variance in fertility was highest. Hence, variation in fertility in the older age classes (20-30) was actually responsible for most of the observed variation in fitness among the individuals. Additionally, more than 90% of variation in fitness (lambda) was attributable to individual differences in LRS, whereas only about 5% of all variation in fitness was due to differences in the reproductive schedule. The rate-sensitive fitness measure did not significantly challenge the importance of total fertility as a component of fitness in humans. However, the rate-sensitive measure clearly allowed more accurate estimation of individual fitness, which may be important for answering some more specific questions.

Adaptation, Physiological↗