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Focuses on the limitations of adaptive dynamics as a model of evolution. Information on the distribution of mutational effects; Effects of mutation size on adaptive dynamics; Role of mutation in maintaining genetic variation.

We present two novel methods to infer mating patterns from genetic data. They differ from existing statistical methods of parentage inference in that they apply to populations that deviate from Hardy-Weinberg and linkage equilibrium, and so are suited for the study of assortative mating in hybrid zones. The core data set consists of genotypes at several loci for a number of full-sib clutches of unknown parentage. Our inference is based throughout on estimates of allelic associations within and across loci, such as heterozygote deficit and pairwise linkage disequilibrium. In the first method, the most likely parents of a given clutch are determined from the genotypic distribution of the associated adult population, given an explicit model of nonrandom mating. This leads to estimates of the strength of assortment. The second approach is based solely on the offspring genotypes and relies on the fact that a linear relation exists between associations among the offspring and those in the population of breeding pairs. We apply both methods to a sample from the hybrid zone between the fire-bellied toads Bombina bombina and B. variegata (Anura: Disco glossidae) in Croatia. Consistently, both approaches provide no evidence for a departure from random mating, despite adequate statistical power. Instead, B. variegata-like individuals among the adults contributed disproportionately to the offspring cohort, consistent with their preference for the type of breeding habitat in which this study was conducted.Heredity (2005) 94, 247-257. doi:10.1038/sj.hdy.6800607 Published online 10 November 2004 [ABSTRACT FROM AUTHOR]

We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(Δz) = Σnk=1 FkVA(k), where n is the number of loci contributing to the trait variance, VA(l) = VA is the additive genetic variance, and VA(k) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*A), is closely related to var(Δz); (V*A) = (1 -- F) Σnk=1 kFk-1 VA(k). Thus, epistasis inflates the expected additive variance above VA(1 -- F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*AA<). This is not true in general with diploidy, because dominance alone can reduce (V*A) below VA(1 -- F) (e.g., when dominant... [ABSTRACT FROM AUTHOR]

Abstract Hybridization may influence evolution in a variety of ways. If hybrids are less fit, the geographical range of ecologically divergent populations may be limited, and prezygotic reproductive isolation may be reinforced. If some hybrid genotypes are fitter than one or both parents, at least in some environments, then hybridization could make a positive contribution. Single alleles that are at an advantage in the alternative environment and genetic background will introgress readily, although such introgression may be hard to detect. ‘Hybrid speciation’, in which fit combinations of alleles are established, is more problematic; its likelihood depends on how divergent populations meet, and on the structure of epistasis. These issues are illustrated using Fisher’s model of stabilizing selection on multiple traits, under which reproductive isolation evolves as a side-effect of adaptation in allopatry. This confirms a priori arguments that while recombinant hybrids are less fit on average, some gene combinations may be fitter than the parents, even in the parental environment. Fisher’s model does predict heterosis in diploid F1s, asymmetric incompatibility in reciprocal backcrosses, and (when dominance is included) Haldane’s Rule. However, heterosis arises only when traits are additive, whereas the latter two patterns require dominance. Moreover, because adaptation is via substitutions of small effect, Fisher’s model does not generate the strong effects of single chromosome regions often observed in species crosses. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the impact of diabetes self-management education (DSME) in improving processes and outcomes of diabetes care as measured by a five component diabetes bundle and HbA1c, in individuals with type 2 diabetes mellitus (T2DM)., Methods: A retrospective analysis was performed for adult T2DM patients who received DSME training in 2011-2012 from an accredited American Diabetes Association center at Intermountain Healthcare (IH) and had an HbA1c measurement within the prior 3 months and 2-6 months after completing their first DSME visit. Control patients were selected from the same clinics as case-patients using random number generator to achieve a 1 to 4 ratio. Case and control patients were included if 1) pre-education HbA1c was between 6.0%-14.0%; 2) their main provider was a primary care physician; 3) they met the national Healthcare Effectiveness Data and Information Set criteria for inclusion in the IH diabetes registry. The IH diabetes bundle includes retinal eye exam, nephropathy screening or prescription of angiotensin converting enzyme or angiotensin receptor blocker; blood pressure <140/90 mmHg, LDL <100 mg/dL, HbA1c <8.0%., Results: DSME patients had a significant difference in achievement of the five element IH diabetes bundle and in HbA1c % compared to those without DSME. After adjusting for possible confounders in a multivariate logistic regression model, DSME patients had a 1.5 fold difference in improvement in their diabetes bundle and almost a 3 fold decline in HbA1c compared to the control group., Conclusion: Standardized DSME taught within an IH American Diabetes Association center is strongly associated with a substantial improvement in patients meeting all five elements of a diabetes bundle and a decline in HbA1c beyond usual care. Given the low operating cost of the DSME program, these results strongly support the value adding benefit of this program in treating T2DM patients.

When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are equivalent. Furthermore, the genetic variance that is maintained by mutation-selection balance is [Formula: see text] per locus, where μ is the mutation rate and S the strength of stabilizing selection. In reality, alleles vary in their effects, making the fitness landscape asymmetric and complicating analysis of the equilibria. We show that that the resulting genetic variance depends on the fraction of alleles near fixation, which contribute by [Formula: see text], and on the total mutational effects of alleles that are at intermediate frequency. The interplay between stabilizing selection and mutation leads to a sharp transition: alleles with effects smaller than a threshold value of [Formula: see text] remain polymorphic, whereas those with larger effects are fixed. The genetic load in equilibrium is less than for traits of equal effects, and the fitness equilibria are more similar. We find that if the optimum is displaced, alleles with effects close to the threshold value sweep first, and their rate of increase is bounded by [Formula: see text] Long-term response leads in general to well-adapted traits, unlike the case of equal effects that often end up at a suboptimal fitness peak. However, the particular peaks to which the populations converge are extremely sensitive to the initial states and to the speed of the shift of the optimum trait value., (Copyright © 2014 by the Genetics Society of America.)

Dental caries is an infectious disease that causes tooth decay. The high prevalence of dental caries in recent humans is attributed to more frequent consumption of plant foods rich in fermentable carbohydrates in food-producing societies. The transition from hunting and gathering to food production is associated with a change in the composition of the oral microbiota and broadly coincides with the estimated timing of a demographic expansion in Streptococcus mutans, a causative agent of human dental caries. Here we present evidence linking a high prevalence of caries to reliance on highly cariogenic wild plant foods in Pleistocene hunter-gatherers from North Africa, predating other high caries populations and the first signs of food production by several thousand years. Archaeological deposits at Grotte des Pigeons in Morocco document extensive evidence for human occupation during the Middle Stone Age and Later Stone Age (Iberomaurusian), and incorporate numerous human burials representing the earliest known cemetery in the Maghreb. Macrobotanical remains from occupational deposits dated between 15,000 and 13,700 cal B.P. provide evidence for systematic harvesting and processing of edible wild plants, including acorns and pine nuts. Analysis of oral pathology reveals an exceptionally high prevalence of caries (51.2% of teeth in adult dentitions), comparable to modern industrialized populations with a diet high in refined sugars and processed cereals. We infer that increased reliance on wild plants rich in fermentable carbohydrates and changes in food processing caused an early shift toward a disease-associated oral microbiota in this population.

Presents an analysis of hybrid zones. Significance of hybrid zones to taxonomists; Appearance of a wide range of genotypes found in a hybrid zone; Discussion on the relation of hybrid zones with speciation and the shifting balance.

Focuses on the study concerning genetic revolutions and gene speciation. Usability of adaptive landscape to classify different models of speciation; Implications of the study for the founder effects and genetic evolutions; Changes in the selection pressures and genetic driffs.

Discusses evolutionary quantitative genetics. Genetics of quantitative variation; Differences of between populations; Paradox of per-character versus per-locus mutation rates; Estimation of fitness and application of models to microevolution and macroevolution.

Objective: To compare the efficacy of mannose-terminated glucocerbrosidase prepared from natural (alglucerase; Ceredase, Genzyme Corp., Cambridge, Massachusetts) and recombinant (imiglucerase; Cerezyme, Genzyme Corp.) sources in treating type 1 Gaucher disease.Design: Double-blind, randomized, parallel trial.Setting: University medical center and clinical research hospital.Patients: 15 patients (4 children and 11 adults) randomly assigned to receive Ceredase and 15 patients (3 children and 12 adults) assigned to receive Cerezyme.Intervention: Ceredase and Cerezyme were infused every 2 weeks for 9 months at a dose of 60 U/kg body weight.Outcome Measures: Hemoglobin levels, platelet counts, and serum acid phosphatase and angiotensin-converting enzyme activities were monitored every 2 weeks during the trial. Hepatic and splenic volumes were assessed at the time of randomization and after 6 and 9 months of enzyme infusion. Formation of IgG antibodies to Ceredase or Cerezyme was monitored every 3 months by radioimmunoprecipitation assay.Results: No significant differences were found in the rate or extent of improvement in hemoglobin levels, platelet counts, serum acid phosphatase or angiotensin-converting enzyme activities, or hepatic or splenic volumes between either treatment group. The incidence of IgG antibody formation was greater in the Ceredase group (40%) than in the Cerezyme group (20%). No major immunologic adverse events occurred in either group.Conclusions: Our study shows the therapeutic similarity of Ceredase and Cerezyme. Cerezyme has the advantage of being theoretically unlimited in supply and free of potential pathogenic contaminants. [ABSTRACT FROM AUTHOR]

We prospectively applied a protocol used to sedate children who required a liver biopsy. Sixty liver biopsies were performed on thirty pediatric patients to assess the effects of treatment. Sixteen patients had Type 1 Gaucher's disease of which seven had a platelet count between 50-100,000/mm3. All seven had bleeding time performed and when indicated, intravenous DDAVP (1-deamino-8-D-arginine vasopressin) was used to improve hemostasis. Fourteen patients had Niemann-Pick disease type C of which eight were significantly demented and uncooperative. Before liver biopsy, all patients were sedated with the following regimen: oral chlorpromazine (1 mg/kg) followed one hour later by intravenous meperidine (1 mg/kg) and pentobarbital (maximum dosage 6 mg/kg) administered by slow intravenous injection. Liver biopsies were obtained safely on all patients. Only 1 patient (2%) developed a potentially serious complication: an obstructed airway which was readily corrected by simple repositioning. Transient less serious complications occurred in another 7 patients (12%). There was no long term sequalae of the biopsy procedures. Our study indicates that with appropriate patient selection, this sedation protocol may be useful in pediatric patients requiring a liver biopsy. [ABSTRACT FROM AUTHOR]

A prospective study was performed of 20 consecutive patients with 35 flexor tendon lacerations, in whom post-operative mobilisation was carried out using the Toronto Mobilimb Continuous Passive Motion machine for the first 4 weeks. Overall the results assessed by Buck Gramcko criteria were 17 (85%) excellent or good, 3 (15%) fair and no poor results. Taking the 17 fingers with zone II lacerations, 14 (82%) were excellent or good, 3 (18%) fair and no poor results. [ABSTRACT FROM PUBLISHER]

This paper presents a conformal mapping solution of Laplace's equation in the two dimensional region exterior to two rectangular plates or electrodes at different potentials. Plates with finite and semi-infinite lengths are considered separately and particular emphasis is placed upon the case when the separation between the plates is small. The key results of the paper are expressions for the integral of the square of the normal field along the mid-line between the plates. This integral is of importance in certain gaseous conductor experiments that are sufficiently accurate for a consideration of end effects to be necessary. For small gaps, the dominant end correction to the integral is linear with the gap width. It is also shown that, for small gaps, the simplified (semi-infinite) geometry gives essentially the same value for the integral as the full (finite plate length) geometry. [ABSTRACT FROM PUBLISHER]

The classic problem, first treated by Taylor [18], of the dispersion of inert soluble matter in fluid flow continues to attract attention from researchers describing the approach to the asymptotic state [5, 17]. The present article considers some of the complications caused when the solute is chemically active, Dispersing chemically active solutes occur in diverse fields such as chromatography, chemical engineering and environmental fluid mechanics.The asymptotic large-time analysis of Chatwin [5] is re-worked to handle the case of reactive solutes dispersing in parallel flow. Matching between moderate and large-time solutions requires consideration of the integral moments of the reactive contaminant could, and the Aris method of moments is therefore invoked and modified for reaction effects. The results are applied in detail to the outstanding paractical example—the chemical flow reactor (a device used to measure reaction rates for chemical reactions taking place between fluids). For this case, the paper provides a practical alternative to recent variable diffusion coefficient studies [6, 7, 15], and presents further results for the concentration distribution and for the limiting behaviour under weak and vigorous recactions at the boundary of the flow. [ABSTRACT FROM PUBLISHER]

The dispersion of a passive solute in three-dimensional flow is examined for short times after the injection of solute. If the diffusivity is constant, the solute at first diffuses isotropically about the fluid particle originally coincident with the injection point whilst, at longer times, the effect of diffusion across a velocity shear becomes more important. An asymptotic expansion is derived for the concentration of solute at small times after its injection into the fluid flow and the use of the theory is illustrated for three representative flows. Some critical remarks on the applicability and limitations of the results conclude the note. [ABSTRACT FROM PUBLISHER]

An interior layer problem posed by an elliptic partial differential equation of the type ε∇2φ - x∂φ/∂y = f(x, y, ε), 0 < ε ≪ 1, is investigated. This equation arises, for example, in the theory of rotating fluids and the important feature of the problem is an interior layer of width O(ε1/3) in which the solution has a relatively large magnitude.The paper considers the simplest case which involves an interior layer, that is, where the domain is rectangular and f(x, y, ε) = εA for A constant. A leading approximation is derived and it is shown to be asymptotic to the exact solution in nearly all of the domain as ε → 0. The error estimates are derived using an a priori estimate for the solution of elliptic equations and a technique which optimizes the estimates is introduced. The applicability and limitations of the estimation technique are discussed briefly. [ABSTRACT FROM PUBLISHER]

The purpose of this paper is to describe the radiographic findings in type 3 b Gaucher disease, a chronic neuronopathic form of the illness with severe systemic manifestations. Between 1980 and 1985 17 consecutive patients were evaluated with radiography of the chest, long bones and spine, CT of the head and chest, abdominal sonography, and MRI of the head, abdomen and spine. Clinical manifestations were severe, and led to death from hepatic, pulmonary or cardiac failure in nine patients. Type 3 b Gaucher disease shares the same spectrum of radiographic findings observed in type 1 disease, but the systemic manifestations are more severe. Pulmonary infiltrates, thoracic lymph node enlargement, vertebral compression fractures and osteonecrosis of the long bones occur much more frequently in patients with type 3 b disease. [ABSTRACT FROM AUTHOR]

Two forms of treatment of Kienbck’s disease were compared in a total of thirty-seven wrists. Sixteen had been treated conservatively and were followed-up for an average of twenty years. Twenty-one had undergone silicone replacement arthroplasty an average of five years prior to review. Clinical results of conservative treatment showed four (25%) good, six (37.5%) fair and six (37.5%) with a poor result. Radiological deterioration was seen in only a quarter of cases. After silicone replacement there were nine (43%) good and seven (33%) fair. Five (24%) cases had a very poor result associated with dislocation of the prosthesis but design improvements have made this less frequent. Radiological abnormalities were noted in more than half of cases treated by silicone replacement arthroplasty. These included carpal collapse, scapho-lunate diastasis and generalised degenerative changes in the carpus. There were two cases with cyst formation in the capitate which closely resembled previous reports of silicone synovitis. [ABSTRACT FROM PUBLISHER]

Twenty patients with Dupuytren’s disease arising from the abductor digiti minimi have been studied. The different patterns of origin, course, and termination of the diseased cord are described, and the clinical implications discussed. [ABSTRACT FROM PUBLISHER]

Fifty-four patients with fifty-nine intra-articular fractures of the phalanges have been followed prospectively for eleven years, at the end of which time only four had significant pain and sixteen others discomfort in cold weather. Improvement in the symptoms and in the range of motion often continued for more than a year after injury. Although 17% of joints developed minor osteophytes or cysts, only one had both radiological evidence of arthritis and persistent pain. [ABSTRACT FROM PUBLISHER]

The results of treatment in 50 consecutive patients with established non-union of the scaphoid are presented. All patients were treated under the care of a single consultant, for the same indications. Russe bone graft is compared with wedge bone graft plus Herbert screw fixation, in terms of union and function. Overall, a higher success rate was obtained by wedge graft plus Herbert screw, and a significantly better range of movement. However, Russe bone graft appears equally satisfactory for fibrous non-union. [ABSTRACT FROM PUBLISHER]

Sixteen arms in eight cadavers were dissected. The extensor pollicis brevis followed the description given in standard anatomy texts in only three out of the sixteen arms. Four out of the eight cadavers showed asymmetry of the extensor pollicis brevis between their two sides. [ABSTRACT FROM PUBLISHER]