4,134 research outputs found

    Solitons in quadratic nonlinear photonic crystals

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    We study solitons in one-dimensional quadratic nonlinear photonic crystals with modulation of both the linear and nonlinear susceptibilities. We derive averaged equations that include induced cubic nonlinearities and numerically find previously unknown soliton families. The inclusion of the induced cubic terms enables us to show that solitons still exist even when the effective quadratic nonlinearity vanishes and conventional theory predicts that there can be no soliton. We demonstrate that both bright and dark forms of these solitons are stable under propagation.Comment: 4 pages with 6 figure

    Identification of nuclear factors which interact with the 5′ flanking region of the EF-1αO gene in Xenopus laevis

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    AbstractThe EF-1αO gene of Xenopus laevis is a stage-specific gene, being transcribed in oogonia and oocytes, but not in postmeiotic germ cells and terminally differentiated cells. We found that two trans-acting factors from oocyte nuclear extract are able to interact with a DNA sequence in the 5′-upstream region of the EF-1αO gene. Methylation interference experiments suggested that the two factors recognised the same DNA element. Gel retardation assays indicated that part of the protein binding site could be confined to a 21 bp sequence, located between −51 and −72, relative to the cap site. Interestingly, this region shares great homology to a negative regulatory segment in the promoter of the TFIIIA gene, another developmentally regulated gene

    Genetic architecture of adaptive radiation across two trophic levels

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    Evolution of trophic diversity is a hallmark of adaptive radiation. Yet, transitions between carnivory and herbivory are rare in young adaptive radiations. Haplochromine cichlid fish of the African Great Lakes are exceptional in this regard. Lake Victoria was colonized by an insectivorous generalist and in less than 20 000 years, several clades of specialized herbivores evolved. Carnivorous versus herbivorous lifestyles in cichlids require many different adaptations in functional morphology, physiology and behaviour. Ecological transitions in either direction thus require many traits to change in a concerted fashion, which could be facilitated if genomic regions underlying these traits were physically linked or pleiotropic. However, linkage/pleiotropy could also constrain evolvability. To investigate components of the genetic architecture of a suite of traits that distinguish invertivores from algae scrapers, we performed quantitative trait locus (QTL) mapping using a second-generation hybrid cross. While we found indications of linkage/pleiotropy within trait complexes, QTLs for distinct traits were distributed across several unlinked genomic regions. Thus, a mixture of independently segregating variation and some pleiotropy may underpin the rapid trophic transitions. We argue that the emergence and maintenance of associations between the different genomic regions underpinning co-adapted traits that evolved and persist against some gene flow required reproductive isolation

    Estimating and Comparing Health and Financial Risk Protection Outcomes in Economic Evaluations

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    Objectives Improving health and financial risk protection (FRP, the prevention of medical impoverishment) and their distributions is a major objective of national health systems. Explicitly describing FRP and disaggregated (eg, across socioeconomic groups) impact of health interventions in economic evaluations can provide decision makers with a broader set of health and financial outcomes to compare and prioritize interventions against each other. Methods We propose methods to synthesize such a broader set of outcomes by estimating and comparing the distributions in both health and FRP benefits procured by health interventions. We build on benefit-cost analysis frameworks and utility-based models, and we illustrate our methods with the case study of universal public finance (financing by government regardless of whom an intervention is targeting) of disease treatment in a low- and middle-income country setting. Results Two key findings seem to emerge: FRP is critical when diseases are less lethal (eg, case fatality rates <1% or so), and quantitative valuation of inequality aversion across income groups matters greatly. We recommend the use of numerous sensitivity analyses and that all distributional health and financial outcomes be first presented in a disaggregated form (before potential subsequent aggregation). Conclusions Estimation approaches such as the one we propose provide explicit disaggregated considerations of equity, FRP, and poverty impact for the development of health sector policies, with high relevance for population-based preventive measures.publishedVersio

    PET kinetics of radiolabeled antidepressant, [N-methyl-11C]mirtazapine, in the human brain

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    BACKGROUND: We compared six kinetic models with and without the requirement of arterial cannulation for estimating the binding potential of [N-methyl-(11)C]mirtazapine in the living human brain. METHODS: Distribution volumes of [N-methyl-(11)C]mirtazapine in brain regions were estimated using single- and two-tissue compartment models as well as a graphical plasma input model. The two-tissue compartment model provided a direct estimate of the binding potentials of [N-methyl-(11)C]mirtazapine in brain regions, while binding potentials of the single-tissue compartment model and the graphical plasma input model were estimated indirectly from ratios of distribution volumes in brain regions. We obtained also direct estimates of binding potentials using a graphical reference tissue model and two nonlinear reference tissue models. RESULTS: The two-tissue compartment model required several fits with different initial guesses for avoiding negative values of parameters. Despite the extra fits, estimates of distribution volumes and binding potentials of [N-methyl-(11)C]mirtazapine obtained by the two-tissue compartment model were far more variable than those produced by the other methods. The graphical plasma input method and the graphical reference tissue method provided estimates of the binding potential that correlated closely, but differed in magnitude. The single-tissue compartment model provided relatively low estimates of binding potentials with curves that failed to fit the data as well as the three other methods that used the entire series of positron emission tomography data. The reference tissue method and the simplified reference tissue method provided similar, consistent estimates of binding potentials. However, certain assumptions of the simplified reference tissue method may not be fulfilled by the radioligand. CONCLUSION: The reference tissue method is appropriate for estimating the binding potential of [N-methyl-(11)C]mirtazapine in regions of the human brain so that the binding potential of [N-methyl-(11)C]mirtazapine can be estimated without arterial cannulation

    Genomic prediction when some animals are not genotyped

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    <p>Abstract</p> <p>Background</p> <p>The use of genomic selection in breeding programs may increase the rate of genetic improvement, reduce the generation time, and provide higher accuracy of estimated breeding values (EBVs). A number of different methods have been developed for genomic prediction of breeding values, but many of them assume that all animals have been genotyped. In practice, not all animals are genotyped, and the methods have to be adapted to this situation.</p> <p>Results</p> <p>In this paper we provide an extension of a linear mixed model method for genomic prediction to the situation with non-genotyped animals. The model specifies that a breeding value is the sum of a genomic and a polygenic genetic random effect, where genomic genetic random effects are correlated with a genomic relationship matrix constructed from markers and the polygenic genetic random effects are correlated with the usual relationship matrix. The extension of the model to non-genotyped animals is made by using the pedigree to derive an extension of the genomic relationship matrix to non-genotyped animals. As a result, in the extended model the estimated breeding values are obtained by blending the information used to compute traditional EBVs and the information used to compute purely genomic EBVs. Parameters in the model are estimated using average information REML and estimated breeding values are best linear unbiased predictions (BLUPs). The method is illustrated using a simulated data set.</p> <p>Conclusions</p> <p>The extension of the method to non-genotyped animals presented in this paper makes it possible to integrate all the genomic, pedigree and phenotype information into a one-step procedure for genomic prediction. Such a one-step procedure results in more accurate estimated breeding values and has the potential to become the standard tool for genomic prediction of breeding values in future practical evaluations in pig and cattle breeding.</p

    Cost-effectiveness of medical interventions to prevent cardiovascular disease in a sub-Saharan African country – the case of Tanzania

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    BACKGROUND: There is a high and rising prevalence of cardiovascular risk in sub-Saharan Africa, a development typical for countries in epidemiological transition. Contrary to recommendations in treatment guidelines, medical interventions to prevent cardiovascular disease are implemented only on a limited scale in these settings. There is a widespread concern that such treatment is not cost-effective compared to alternative health interventions. The main objectives of this article are therefore to calculate costs-, effects and cost-effectiveness of fourteen medical interventions of primary prevention of cardiovascular disease in Tanzania, including Acetylsalicylic acid, a diuretic drug (Hydrochlorothiazide), a β-blocker (Atenolol), a calcium channel blocker (Nifedepine), a statin (Lovastatin) and various combinations of these. METHODS: Effect sizes were derived from systematic reviews or meta-analyses, and calculated as Disability Adjusted Life Years (DALYs). Data on drug costs were calibrated to a Tanzanian setting. Other recurrent and capital costs were derived from previous studies and reviewed by local experts. Expected lifetime costs and health outcomes were calculated using a life-cycle model. Probabilistic cost-effectiveness analysis was performed using Monte Carlo simulation, and results presented as cost-effectiveness acceptability curves and frontiers. The potential impacts of uncertainty in value laden single parameters were explored in one-way sensitivity analyses. RESULTS: The incremental cost-effectiveness ratios for the fourteen interventions and four different levels of risk (totally 56 alternative interventions) ranged from about USD 85 per DALY to about USD 4589 per DALY saved. Hydrochlorothiazide as monotherapy is the drug yielding the most favorable cost-effectiveness ratio, although not significantly lower than when it is combined in duo-therapy with Aspirin or a β-blocker, in triple-therapy with Aspirin and a β-blocker, or than Aspirin given as mono-therapy. CONCLUSION: Preventive cardiology is not cost-effective for any patient group in this setting until willingness to pay exceeds USD 85 per DALY. At this level of willingness to pay, the optimal intervention is Hydrochlorothiazide to patients with very high cardiovascular risk. As willingness to pay for health increase further, it becomes optimal to provide this treatment also to patients with lower cardiovascular risk, and to substitute to more sophisticated interventions
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