Re-interpreting conventional interval estimates taking into account bias and extra-variation

BACKGROUND: The study design with the smallest bias for causal inference is a perfect randomized clinical trial. Since this design is often not feasible in epidemiologic studies, an important challenge is to model bias properly and take random and systematic variation properly into account. A value for a target parameter might be said to be "incompatible" with the data (under the model used) if the parameter's confidence interval excludes it. However, this "incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We propose the following way of re-interpreting conventional results. Given a specified focal value for a target parameter (typically the null value, but possibly a non-null value like that representing a twofold risk), the difference between the focal value and the nearest boundary of the confidence interval for the parameter is calculated. This represents the maximum correction of the interval boundary, for bias and extra-variation, that would still leave the focal value outside the interval, so that the focal value remained "incompatible" with the data. We describe a short example application concerning a meta analysis of air versus pure oxygen resuscitation treatment in newborn infants. Some general guidelines are provided for how to assess the probability that the appropriate correction for a particular study would be greater than this maximum (e.g. using knowledge of the general effects of bias and extra-variation from published bias-adjusted results). SUMMARY: Although this approach does not yet provide a method, because the latter probability can not be objectively assessed, this paper aims to stimulate the re-interpretation of conventional confidence intervals, and more and better studies of the effects of different biases

Recent Developments in the General Atomic and Molecular Electronic Structure System

A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized

Hierarchical Models in the Brain

This paper describes a general model that subsumes many parametric models for continuous data. The model comprises hidden layers of state-space or dynamic causal models, arranged so that the output of one provides input to another. The ensuing hierarchy furnishes a model for many types of data, of arbitrary complexity. Special cases range from the general linear model for static data to generalised convolution models, with system noise, for nonlinear time-series analysis. Crucially, all of these models can be inverted using exactly the same scheme, namely, dynamic expectation maximization. This means that a single model and optimisation scheme can be used to invert a wide range of models. We present the model and a brief review of its inversion to disclose the relationships among, apparently, diverse generative models of empirical data. We then show that this inversion can be formulated as a simple neural network and may provide a useful metaphor for inference and learning in the brain

Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids

[EN] Hybridization between tetraploids and its related diploids is generally unsuccessful in Centaurea, hence natural formation of triploid hybrids is rare. In contrast, the diploid Centaurea aspera and the allotetraploid C. seridis coexist in several contact zones where a high frequency of triploid hybrids is found. We analyzed the floral biology of the three taxa to identify reproductive isolation mechanisms that allow their coexistence. Flowering phenology was recorded, and controlled pollinations within and between the three taxa were performed in the field. Ploidy level and germination of progeny were also assessed. There was a 50% flowering overlap which indicated a phenological shift. Diploids were strictly allogamous and did not display mentor effects, while tetraploids were found to be highly autogamous. This breakdown of self-incompatibility by polyploids is first described in Centaurea. The asymmetrical formation of the hybrid was also found: all the triploid intact cypselae came from the diploid mothers pollinated by the pollen of tetraploids. Pollen and eggs from triploids were totally sterile, acting as a strong triploid block. These prezygotic isolation mechanisms ensured higher assortative mating in tetraploids than in diploids, improving its persistence in the contact zones. However these mechanisms can also be the cause of the low genetic diversity and high genetic structure observed in C. seridis.Ferriol Molina, M.; Garmendia, A.; Ana Gonzalez; Merle Farinós, HB. (2015). Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids. PLoS ONE. 10(10):1-13. doi:10.1371/journal.pone.0140465S1131010Jiao, Y., Wickett, N. J., Ayyampalayam, S., Chanderbali, A. S., Landherr, L., Ralph, P. E., … dePamphilis, C. W. (2011). Ancestral polyploidy in seed plants and angiosperms. Nature, 473(7345), 97-100. doi:10.1038/nature09916Wood, T. E., Takebayashi, N., Barker, M. S., Mayrose, I., Greenspoon, P. B., & Rieseberg, L. H. (2009). The frequency of polyploid speciation in vascular plants. Proceedings of the National Academy of Sciences, 106(33), 13875-13879. doi:10.1073/pnas.0811575106ROMASCHENKO, K., ERTUǦRUL, K., SUSANNA, A., GARCIA-JACAS, N., UYSAL, T., & ARSLAN, E. (2004). New chromosome counts in the Centaurea Jacea group (Asteraceae, Cardueae) and some related taxa. Botanical Journal of the Linnean Society, 145(3), 345-352. doi:10.1111/j.1095-8339.2004.00292.xHardy, O. J., de Loose, M., Vekemans, X., & Meerts, P. (2001). Allozyme segregation and inter-cytotype reproductive barriers in the polyploid complex Centaurea jacea. Heredity, 87(2), 136-145. doi:10.1046/j.1365-2540.2001.00862.xKOUTECKÝ, P., BAĎUROVÁ, T., ŠTECH, M., KOŠNAR, J., & KARÁSEK, J. (2011). Hybridization between diploidCentaurea pseudophrygiaand tetraploidC. jacea(Asteraceae): the role of mixed pollination, unreduced gametes, and mentor effects. Biological Journal of the Linnean Society, 104(1), 93-106. doi:10.1111/j.1095-8312.2011.01707.xKoutecký, P. (2012). A diploid drop in the tetraploid ocean: hybridization and long-term survival of a singular population of Centaurea weldeniana Rchb. (Asteraceae), a taxon new to Austria. Plant Systematics and Evolution, 298(7), 1349-1360. doi:10.1007/s00606-012-0641-5Mráz, P., Španiel, S., Keller, A., Bowmann, G., Farkas, A., Šingliarová, B., … Müller-Schärer, H. (2012). Anthropogenic disturbance as a driver of microspatial and microhabitat segregation of cytotypes of Centaurea stoebe and cytotype interactions in secondary contact zones. Annals of Botany, 110(3), 615-627. doi:10.1093/aob/mcs120Olšavská, K., & Löser, C. J. (2013). Mating System and Hybridization of the Cyanus triumfetti and C. montanus Groups (Asteraceae). Folia Geobotanica, 48(4), 537-554. doi:10.1007/s12224-013-9155-3Španiel, S., Marhold, K., Hodálová, I., & Lihová, J. (2008). Diploid and Tetraploid Cytotypes of Centaurea stoebe (Asteraceae) in Central Europe: Morphological Differentiation and Cytotype Distribution Patterns. Folia Geobotanica, 43(2), 131-158. doi:10.1007/s12224-008-9008-7HARDY, O. J., VANDERHOEVEN, S., DE LOOSE, M., & MEERTS, P. (2000). Ecological, morphological and allozymic differentiation between diploid and tetraploid knapweeds (Centaurea jacea) from a contact zone in the Belgian Ardennes. New Phytologist, 146(2), 281-290. doi:10.1046/j.1469-8137.2000.00631.xFerriol, M., Garmendia, A., Ruiz, J. J., Merle, H., & Boira, H. (2012). Morphological and molecular analysis of natural hybrids between the diploidCentaurea asperaL. and the tetraploidC. seridisL. (Compositae). Plant Biosystems - An International Journal Dealing with all Aspects of Plant Biology, 146(sup1), 86-100. doi:10.1080/11263504.2012.727878Ferriol, M., Merle, H., & Garmendia, A. (2014). Microsatellite evidence for low genetic diversity and reproductive isolation in tetraploidCentaurea seridis(Asteraceae) coexisting with diploidCentaurea asperaand triploid hybrids in contact zones. Botanical Journal of the Linnean Society, 176(1), 82-98. doi:10.1111/boj.12194Garmendia, A., Ferriol, M., Juarez, J., Zając, A., Kałużny, K., & Merle, H. (2015). A rare case of a natural contact zone in Morocco between an autopolyploid and an allopolyploid ofCentaurea asperawith sterile tetraploid hybrids. Plant Biology, 17(3), 746-757. doi:10.1111/plb.12284Petit, C., Bretagnolle, F., & Felber, F. (1999). Evolutionary consequences of diploid–polyploid hybrid zones in wild species. Trends in Ecology & Evolution, 14(8), 306-311. doi:10.1016/s0169-5347(99)01608-0Thorsson, A. T., Palsson, S., Sigurgeirsson, A., & Anamthawat-Jonsson, K. (2007). Morphological Variation among Betula nana (diploid), B. pubescens (tetraploid) and their Triploid Hybrids in Iceland. Annals of Botany, 99(6), 1183-1193. doi:10.1093/aob/mcm060Husband And, B. C., & Schemske, D. W. (2000). Ecological mechanisms of reproductive isolation between diploid and tetraploidChamerion angustifolium. Journal of Ecology, 88(4), 689-701. doi:10.1046/j.1365-2745.2000.00481.xKruskal, W. H., & Wallis, W. A. (1952). Use of Ranks in One-Criterion Variance Analysis. Journal of the American Statistical Association, 47(260), 583-621. doi:10.1080/01621459.1952.10483441Dunn, O. J. (1961). Multiple Comparisons among Means. Journal of the American Statistical Association, 56(293), 52-64. doi:10.1080/01621459.1961.10482090HARVILLE, D. A. (1974). Bayesian inference for variance components using only error contrasts. Biometrika, 61(2), 383-385. doi:10.1093/biomet/61.2.383McCullagh, P., & Nelder, J. A. (1989). Generalized Linear Models. doi:10.1007/978-1-4899-3242-6Lambert, D. (1992). Zero-Inflated Poisson Regression, with an Application to Defects in Manufacturing. Technometrics, 34(1), 1. doi:10.2307/1269547Vuong, Q. H. (1989). Likelihood Ratio Tests for Model Selection and Non-Nested Hypotheses. Econometrica, 57(2), 307. doi:10.2307/1912557Ferriol, M., Llorens, L., Gil, L., & Boira, H. (2008). Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L. Plant Systematics and Evolution, 277(1-2), 105-116. doi:10.1007/s00606-008-0110-3Colas, B., Olivieri, I., & Riba, M. (2001). Spatio-temporal variation of reproductive success and conservation of the narrow-endemic Centaurea corymbosa (Asteraceae). Biological Conservation, 99(3), 375-386. doi:10.1016/s0006-3207(00)00229-9Felber, F., & Bever, J. D. (1997). Effect of triploid fitness on the coexistence of diploids and tetraploids. Biological Journal of the Linnean Society, 60(1), 95-106. doi:10.1111/j.1095-8312.1997.tb01485.xPeckert, T., & Chrtek, J. (2006). Mating interactions between coexisting dipoloid, triploid and tetraploid cytotypes ofHieracium Echioides (Asteraceae). Folia Geobotanica, 41(3), 323-334. doi:10.1007/bf02904945HUSBAND, B. C. (2004). The role of triploid hybrids in the evolutionary dynamics of mixed-ploidy populations. Biological Journal of the Linnean Society, 82(4), 537-546. doi:10.1111/j.1095-8312.2004.00339.xStebbins, G. L. (1950). Variation and Evolution in Plants. doi:10.7312/steb94536Barringer, B. C. (2007). Polyploidy and self-fertilization in flowering plants. American Journal of Botany, 94(9), 1527-1533. doi:10.3732/ajb.94.9.1527Borges, L. A., Souza, L. G. R., Guerra, M., Machado, I. C., Lewis, G. P., & Lopes, A. V. (2012). Reproductive isolation between diploid and tetraploid cytotypes of Libidibia ferrea (= Caesalpinia ferrea) (Leguminosae): ecological and taxonomic implications. Plant Systematics and Evolution, 298(7), 1371-1381. doi:10.1007/s00606-012-0643-3Greiner, R., & Oberprieler, C. (2012). The role of inter-ploidy block for reproductive isolation of the diploid Leucanthemum pluriflorum Pau (Compositae, Anthemideae) and its tetra- and hexaploid relatives. Flora - Morphology, Distribution, Functional Ecology of Plants, 207(9), 629-635. doi:10.1016/j.flora.2012.07.001Ferrer, M. M., & Good-Avila, S. V. (2006). Macrophylogenetic analyses of the gain and loss of self-incompatibility in the Asteraceae. New Phytologist, 173(2), 401-414. doi:10.1111/j.1469-8137.2006.01905.xSun, M., & Ritland, K. (1998). Mating system of yellow starthistle (Centaurea solstitialis), a successful colonizer in North America. Heredity, 80(2), 225-232. doi:10.1046/j.1365-2540.1998.00290.xHusband, B. C., & Sabara, H. A. (2003). Reproductive isolation between autotetraploids and their diploid progenitors in fireweed, Chamerion angustifolium (Onagraceae). New Phytologist, 161(3), 703-713. doi:10.1046/j.1469-8137.2004.00998.xAwadalla, P., & Ritland, K. (1997). Microsatellite variation and evolution in the Mimulus guttatus species complex with contrasting mating systems. Molecular Biology and Evolution, 14(10), 1023-1034. doi:10.1093/oxfordjournals.molbev.a025708Reinartz, J. A., & Les, D. H. (1994). Bottleneck-Induced Dissolution of Self-Incompatibility and Breeding System Consequences in Aster furcatus (Asteraceae). American Journal of Botany, 81(4), 446. doi:10.2307/2445494Hiscock, S. J. (2000). Genetic control of self-incompatibility in Senecio squalidus L. (Asteraceae): a successful colonizing species. Heredity, 85(1), 10-19. doi:10.1046/j.1365-2540.2000.00692.xNIELSEN, L. R., SIEGISMUND, H. R., & PHILIPP, M. (2003). Partial self-incompatibility in the polyploid endemic species Scalesia affinis (Asteraceae) from the Galápagos: remnants of a self-incompatibility system? Botanical Journal of the Linnean Society, 142(1), 93-101. doi:10.1046/j.1095-8339.2003.00168.xSonnleitner, M., Weis, B., Flatscher, R., García, P. E., Suda, J., Krejčíková, J., … Hülber, K. (2013). Parental Ploidy Strongly Affects Offspring Fitness in Heteroploid Crosses among Three Cytotypes of Autopolyploid Jacobaea carniolica (Asteraceae). PLoS ONE, 8(11), e78959. doi:10.1371/journal.pone.0078959Cui, C., Ge, X., Gautam, M., Kang, L., & Li, Z. (2012). Cytoplasmic and Genomic Effects on Meiotic Pairing inBrassicaHybrids and Allotetraploids from Pair Crosses of Three Cultivated Diploids. Genetics, 191(3), 725-738. doi:10.1534/genetics.112.140780Comai, L. (2005). The advantages and disadvantages of being polyploid. Nature Reviews Genetics, 6(11), 836-846. doi:10.1038/nrg1711Mráz, P. (2003). Mentor effects in the genusHieracium S.STR. (Compositae, Lactuceae). Folia Geobotanica, 38(3), 345-350. doi:10.1007/bf02803204Husband, B. C., Schemske, D. W., Burton, T. L., & Goodwillie, C. (2002). Pollen competition as a unilateral reproductive barrier between sympatric diploid and tetraploid Chamerion angustifolium. Proceedings of the Royal Society of London. Series B: Biological Sciences, 269(1509), 2565-2571. doi:10.1098/rspb.2002.2196Baldwin, S. J., & Husband, B. C. (2010). Genome duplication and the evolution of conspecific pollen precedence. Proceedings of the Royal Society B: Biological Sciences, 278(1714), 2011-2017. doi:10.1098/rspb.2010.220