An Improved Approximate-Bayesian Model-choice Method for Estimating Shared Evolutionary History

To understand biological diversification, it is important to account for large-scale processes that affect the evolutionary history of groups of co-distributed populations of organisms. Such events predict temporally clustered divergences times, a pattern that can be estimated using genetic data from co-distributed species. I introduce a new approximate-Bayesian method for comparative phylogeographical model-choice that estimates the temporal distribution of divergences across taxa from multi-locus DNA sequence data. The model is an extension of that implemented in msBayes. By reparameterizing the model, introducing more flexible priors on demographic and divergence-time parameters, and implementing a non-parametric Dirichlet-process prior over divergence models, I improved the robustness, accuracy, and power of the method for estimating shared evolutionary history across taxa. The results demonstrate the improved performance of the new method is due to (1) more appropriate priors on divergence-time and demographic parameters that avoid prohibitively small marginal likelihoods for models with more divergence events, and (2) the Dirichlet-process providing a flexible prior on divergence histories that does not strongly disfavor models with intermediate numbers of divergence events. The new method yields more robust estimates of posterior uncertainty, and thus greatly reduces the tendency to incorrectly estimate models of shared evolutionary history with strong support.Comment: 48 pages, 8 figures, 4 tables, 35 pages of supporting information with 1 supporting table and 33 supporting figure

Marginal likelihoods in phylogenetics: a review of methods and applications

By providing a framework of accounting for the shared ancestry inherent to all life, phylogenetics is becoming the statistical foundation of biology. The importance of model choice continues to grow as phylogenetic models continue to increase in complexity to better capture micro and macroevolutionary processes. In a Bayesian framework, the marginal likelihood is how data update our prior beliefs about models, which gives us an intuitive measure of comparing model fit that is grounded in probability theory. Given the rapid increase in the number and complexity of phylogenetic models, methods for approximating marginal likelihoods are increasingly important. Here we try to provide an intuitive description of marginal likelihoods and why they are important in Bayesian model testing. We also categorize and review methods for estimating marginal likelihoods of phylogenetic models, highlighting several recent methods that provide well-behaved estimates. Furthermore, we review some empirical studies that demonstrate how marginal likelihoods can be used to learn about models of evolution from biological data. We discuss promising alternatives that can complement marginal likelihoods for Bayesian model choice, including posterior-predictive methods. Using simulations, we find one alternative method based on approximate-Bayesian computation (ABC) to be biased. We conclude by discussing the challenges of Bayesian model choice and future directions that promise to improve the approximation of marginal likelihoods and Bayesian phylogenetics as a whole.Comment: 33 pages, 3 figure

Implications of uniformly distributed, empirically informed priors for phylogeographical model selection: A reply to Hickerson et al

Establishing that a set of population-splitting events occurred at the same time can be a potentially persuasive argument that a common process affected the populations. Oaks et al. (2013) assessed the ability of an approximate-Bayesian method (msBayes) to estimate such a pattern of simultaneous divergence across taxa, to which Hickerson et al. (2014) responded. Both papers agree the method is sensitive to prior assumptions and often erroneously supports shared divergences; the papers differ about the explanation and solution. Oaks et al. (2013) suggested the method's behavior is caused by the strong weight of uniform priors on divergence times leading to smaller marginal likelihoods of models with more divergence-time parameters (Hypothesis 1); they proposed alternative priors to avoid strongly weighted posteriors. Hickerson et al. (2014) suggested numerical approximation error causes msBayes analyses to be biased toward models of clustered divergences (Hypothesis 2); they proposed using narrow, empirical uniform priors. Here, we demonstrate that the approach of Hickerson et al. (2014) does not mitigate the method's tendency to erroneously support models of clustered divergences, and often excludes the true parameter values. Our results also show that the tendency of msBayes analyses to support models of shared divergences is primarily due to Hypothesis 1. This series of papers demonstrate that if our prior assumptions place too much weight in unlikely regions of parameter space such that the exact posterior supports the wrong model of evolutionary history, no amount of computation can rescue our inference. Fortunately, more flexible distributions that accommodate prior uncertainty about parameters without placing excessive weight in vast regions of parameter space with low likelihood increase the method's robustness and power to detect temporal variation in divergences.Comment: 24 pages, 4 figures, 1 table, 14 pages of supporting information with 10 supporting figure

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment

17α -ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon smallmolecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.Heinz Endowments, the Swiss National Science Foundation, the Steinbrenner Institute for a Steinbrenner Doctoral Fellowship. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)

Where constructionism and critical realism converge: interrogating the domain of epistemological relativism

The paper interrogates the status, nature and significance of epistemological relativism as a key element of constructionism and critical realism. It finds that epistemological relativism is espoused by authorities in critical realism and marginalized or displaced in the field of management and organization studies, resulting in forms of analysis that are empirically, but not fully critically, realist. This evaluation prompts reflection on the question of whether, how and with what implications epistemological relativism might be recast at the heart of critical realist studies of management and organization

Diabetes and pancreatic cancer survival: A prospective cohort-based study

BACKGROUND: Diabetes is a risk factor for pancreatic cancer but its association with survival from pancreatic cancer is poorly understood. Our objective was to investigate the association of diabetes with survival among pancreatic cancer patients in a prospective cohort-based study where diabetes history was ascertained before pancreatic cancer diagnosis. METHODS: We evaluated survival by baseline (1993–2001) self-reported diabetes history (n=62) among 504 participants that developed exocrine pancreatic cancer within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards model, adjusted for age, sex, body mass index, race, smoking, and tumour stage (local, locally advanced, and metastatic). RESULTS: The multivariable-adjusted HR for mortality comparing participants with diabetes to those without was 1.52 (95% CI=1.14–2.04, P-value <0.01). After excluding those diagnosed with pancreatic cancer within 3 years of study enrolment, HR for mortality among those with diabetes was 1.45 (95% CI=1.06–2.00, P-value=0.02). CONCLUSIONS: Using prospectively collected data, our findings indicate that diabetes is associated with worse survival among patients with pancreatic cancer

Coalescent-based species delimitation in the sand lizards of the Liolaemus wiegmannii complex (Squamata: Liolaemidae)

Coalescent-based algorithms coupled with the access to genome-wide data have become powerful tools forassessing questions on recent or rapid diversification, as well as delineating species boundaries in the absence of reciprocal monophyly. In southern South America, the diversification of Liolaemus lizards during the Pleistocene is well documented and has been attributed to the climatic changes that characterized this recent period of time. Past climatic changes had harsh effects at extreme latitudes, including Patagonia, but habitat changes at intermediate latitudes of South America have also been recorded, including expansion of sand fields over northern Patagonia and Pampas). In this work, we apply a coalescent-based approach to study the diversification of the Liolaemus wiegmannii species complex, a morphologically conservative clade that inhabits sandy soils across northwest and south-central Argentina, and the south shores of Uruguay. Using four standard sequence markers (mitochondrial DNA and three nuclear loci) along with ddRADseq data we inferred species limits and a time calibrated species tree for the L. wiegmannii complex in order to evaluate the influence of Quaternary sand expansion/retraction cycles on diversification. We also evaluated the evolutionary independence of the recently described L. gardeli and inferred its phylogenetic position relative to L. wiegmannii. We find strong evidence for six allopatric candidate species within L. wiegmannii, which diversified during the Pleistocene. The Great Patagonian Glaciation (∼1 million years before present) likely split the species complex into two main groups: one composed of lineages associated with sub-Andean sedimentary formations, and the other mostly related to sand fields in the Pampas and northern Patagonia. We hypothesize that early speciation within L. wiegmannii was influenced by the expansion of sand dunes throughout central Argentina and Pampas. Finally, L. gardeli is supported as a distinct lineage nested within the L. wiegmannii complex.Fil: Villamil, Joaquín. Universidad de la República. Facultad de Ciencias; UruguayFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Sites, Jack W.. University Brigham Young; Estados UnidosFil: Leaché, Adam D.. University of Washington; Estados UnidosFil: Maneyro, Raúl. Universidad de la República. Facultad de Ciencias; UruguayFil: Camargo Bentaberry, Arley. Universidad de la República; Urugua