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In hyperglycemia, the serum sodium concentration ( [Na] S ) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na] S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na] S , which results in a [Na] S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ( [Glu] S ) and [Na] S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu] S and [Na] S , those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal-ligand complexes, especially with repeated use, should be studied further., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Motivation: Consensus methods can be used for reconstructing a species tree from several gene trees, which exhibit incompatible topologies due to incomplete lineage sorting. Motivated by the fact that there are no anomalous rooted gene trees with three taxa and no anomalous unrooted gene trees with four taxa in the multispecies coalescent model, several contemporary methods form the gene tree consensus by finding the median tree with respect to the triplet or quartet distance-i.e. estimate the species tree as the tree which minimizes the sum of triplet or quartet distances to the input gene trees. These methods reformulate the solution to the consensus problem as the solution to a recursively solved dynamic programming (DP) problem. We present an iterative, easily parallelizable approach to finding the exact median triplet tree and implement it as an open source software package that can also find suboptimal consensus trees within a specified triplet distance to the gene trees. The most time-consuming step for methods of this type is the creation of a weights array for all possible subtree bipartitions. By grouping the relevant calculations and array update operations of different bipartitions of the same subtree together, this implementation finds the exact median tree of many gene trees faster than comparable methods, has better scaling properties with respect to the number of gene trees and has a smaller memory footprint., Results: RTIST (Rooted Triple Inference of Species Trees) finds the exact median triplet tree of a set of gene trees. Its runtime and memory footprints scale better than existing algorithms. RTIST can resolve all the non-unique median trees, as well as sub-optimal consensus trees within a user-specified triplet distance to the median. Although it is limited in the number of taxa (≤20), its runtime changes little when the number of gene trees is changed by several orders of magnitude., Availability and Implementation: RTIST is written in C and Python. It is freely available at https://github.com/glebzhelezov/rtist., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Species trees that can generate a nonmatching gene tree topology that is more probable than the topology matching the species tree are said to be in an anomaly zone. We introduce some heuristic approaches to infer whether species trees are in anomaly zones when it is difficult or impossible to compute the entire distribution of gene tree topologies. Here, probabilities of unrooted, unranked, and ranked gene tree topologies under the multispecies coalescent are used. A ranked tree can be viewed as an unranked tree with a temporal ordering of its internal nodes. Overall, considering probabilities of unrooted or unranked gene tree topologies within one nearest neighbor interchange from the species tree topology is a reasonable heuristic to infer the existence of anomalous unrooted or unranked gene trees, respectively. We investigated a test proposed by Linkem et al. (2016) which classifies a species tree as being in an unranked anomaly zone if there is a subset of four taxa in an unranked anomaly zone. We find this test to have high true positive rates, but it can also have high false positive rates. For ranked trees, because at least one of the most probable ranked gene tree topologies must have the same unranked topology as the species tree, we propose to use only those ranked gene trees that have topologies that match the unranked species tree topology. We find that the probability that the species tree is in unrooted and unranked anomaly zones tends to increase with the speciation rate, and the probability of all three types of anomaly zones increases rapidly with the number of taxa. We find that probabilities that species trees are in an anomaly zone can be quite high for moderately high speciation rates., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Species trees, which describe the evolutionary relationships between species, are often inferred from gene trees, which describe the ancestral relationships between sequences sampled at different loci from the species of interest. A common approach to inferring species trees from gene trees is motivated by supposing that gene tree variation is due to incomplete lineage sorting, also known as deep coalescence. One of the earliest methods motivated by deep coalescence is to find the species tree that minimizes the number of deep coalescent events needed to explain discrepancies between the species tree and input gene trees. This minimize deep coalescence (MDC) criterion can be applied in both rooted and unrooted settings. where either rooted or unrooted gene trees can be used to infer a rooted species tree. Previous work has shown that MDC is statistically inconsistent in the rooted setting, meaning that under a probabilistic model for deep coalescence, the multispecies coalescent, for some species trees, increasing the number of input gene trees does not make the method more likely to return a correct species tree. Here, we obtain analogous results in the unrooted setting, showing conditions leading to inconsistency of the MDC criterion using the multispecies coalescent model with unrooted gene trees for four taxa and five taxa., Competing Interests: The authors have declared that no competing interests exist.

Summary: PRANC computes the Probabilities of RANked gene tree topologies under the multispecies coalescent. A ranked gene tree is a gene tree accounting for the temporal ordering of internal nodes. PRANC can also estimate the maximum likelihood (ML) species tree from a sample of ranked or unranked gene tree topologies. It estimates the ML tree with estimated branch lengths in coalescent units., Availability and Implementation: PRANC is written in C++ and freely available at github.com/anastasiiakim/PRANC., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A labeled gene tree topology that is more probable than the labeled gene tree topology matching a species tree is called "anomalous." Species trees that can generate such anomalous gene trees are said to be in the "anomaly zone." Here, probabilities of "unranked" and "ranked" gene tree topologies under the multispecies coalescent are considered. A ranked tree depicts not only the topological relationship among gene lineages, as an unranked tree does, but also the sequence in which the lineages coalesce. In this article, we study how the parameters of a species tree simulated under a constant-rate birth-death process can affect the probability that the species tree lies in the anomaly zone. We find that with more than five taxa, it is possible for species trees to have both anomalous unranked and ranked gene trees. The probability of being in either type of anomaly zone increases with more taxa. The probability of anomalous gene trees also increases with higher speciation rates. We observe that the probabilities of unranked anomaly zones are higher and grow much faster than those of ranked anomaly zones as the speciation rate increases. Our simulation shows that the most probable ranked gene tree is likely to have the same unranked topology as the species tree. We design the software PRANC, which computes probabilities of ranked gene tree topologies given a species tree under the coalescent model., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Over the past decade, many states have developed approaches to reimburse for immediate postpartum long-acting reversible contraception. Despite expanded coverage, few hospitals offer immediate postpartum long-acting reversible contraception., Objectives: Immediate postpartum long-acting reversible contraception implementation is complex and requires a committed multidisciplinary team. After New Mexico Medicaid approved reimbursement for this service, the New Mexico Perinatal Collaborative developed and initiated an evidence-based implementation program containing several components. We sought to evaluate timing of the implementation process and facilitators and barriers to immediate postpartum long-acting reversible contraception in several New Mexico rural hospitals. The primary study outcome was time from New Mexico Perinatal Collaborative program component introduction in each hospital to the hospital's completion of the corresponding implementation step. Secondary outcomes included barriers and facilitators to immediate postpartum contraception implementation., Study Design: In this mixed-methods study, conducted from April 2017 to May 2018, we completed semistructured questionnaires and interviews with 20 key personnel from 7 New Mexico hospitals that planned to implement immediate postpartum long-acting reversible contraception. The New Mexico Perinatal Collaborative introduced program components to hospitals in a stepped-wedge design. Participants contributed baseline and follow-up data at 4 time periods detailing the steps taken towards program implementation and the timing of step completion at their hospital. Qualitative data were analyzed using directed qualitative content analysis principles based on the Consolidated Framework for Implementation Research., Results: Investigators conducted 43 interviews during the 14-month study period. Median time to complete steps toward implementation-patient education, clinician training, nursing education, charge capture, available supplies, and protocols or guidelines-ranged from 7 days for clinician training to 357 days to develop patient education materials. Facilitators of immediate postpartum contraception readiness were local hospital clinical champions and institutional administrative and financial stability. Of the 7 hospitals, 4 completed all Perinatal Collaborative implementation program components and 3 of those piloted immediate postpartum long-acting reversible contraception services. Two publicly funded hospitals currently offer immediate postpartum long-acting reversible contraception without verification of payment for the device or insertion. The third hospital piloted the program with 8 contraceptive devices, did not receive reimbursement due to identified flaws in Medicaid billing guidance and does not currently offer the service. The remaining 3 of the 7 hospitals declined to complete the NMPC program; the hospital that completed the program but did not pilot immediate postpartum long-acting reversible contraception did so because Medicaid billing mechanisms were incompatible with their automated billing systems. Participants consistently reported that lack of reimbursement was the major barrier to immediate postpartum long-acting reversible contraception implementation., Conclusion: Despite the New Mexico Perinatal Collaborative's robust implementation process and hospital engagement, most hospitals did not offer immediate postpartum long-acting reversible contraception over the study period. Reimbursement obstacles prevented full service implementation. Interventions to improve immediate postpartum long-acting reversible contraception access must begin with implementation of seamless billing and reimbursement mechanisms to ensure adequate hospital payments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Simultaneously modeling hybridization and the multispecies coalescent is becoming increasingly common, and inference of species networks in this context is now implemented in several software packages. This article addresses some of the conceptual issues and decisions to be made in this modeling, including whether or not to use branch lengths and issues with model identifiability. This article is based on a talk given at a Spotlight Session at Evolution 2017 meeting in Portland, Oregon. This session included several talks about modeling hybridization and gene flow in the presence of incomplete lineage sorting. Other talks given at this meeting are also included in this special issue of Systematic Biology.

The method was proposed by Liu and Yu to infer a species tree topology from unrooted topological gene trees. While its statistical consistency under the multispecies coalescent model was established only for a four-taxon tree, simulations demonstrated its good performance on gene trees inferred from sequences for many taxa. Here, we prove the statistical consistency of the method for an arbitrarily large species tree. Our approach connects to a generalization of the STAR method of Liu, Pearl, and Edwards, and a previous theoretical analysis of it. We further show utilizes only the distribution of splits in the gene trees, and not their individual topologies. Finally, we discuss how multiple samples per taxon per gene should be handled for statistical consistency.

Using topological summaries of gene trees as a basis for species tree inference is a promising approach to obtain acceptable speed on genomic-scale datasets, and to avoid some undesirable modeling assumptions. Here we study the probabilities of splits on gene trees under the multispecies coalescent model, and how their features might inform species tree inference. After investigating the behavior of split consensus methods, we investigate split invariants-that is, polynomial relationships between split probabilities. These invariants are then used to show that, even though a split is an unrooted notion, split probabilities retain enough information to identify the rooted species tree topology for trees of 5 or more taxa, with one possible 6-taxon exception.

Methods for inferring species trees from gene trees motivated by incomplete lineage sorting typically use either rooted gene trees to infer a rooted species tree, or use unrooted gene trees to infer an unrooted species tree, which is then typically rooted using one or more outgroups. Theoretically, however, it has been known since 2011 that it is possible to consistently infer the root of the species tree directly from unrooted gene trees without assuming an outgroup. Here, we use approximate Bayesian computation to infer the root of the species tree from unrooted gene trees assuming the multispecies coalescent model. It is hoped that this approach will be useful in cases where an appropriate outgroup is difficult to find and gene trees do not follow a molecular clock. We use approximate Bayesian computation to infer the root of the species tree from unrooted gene trees. This approach could also be useful when there is prior information that makes a small number of root locations plausible in an unrooted species tree., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recent work in estimating species relationships from gene trees has included inferring networks assuming that past hybridization has occurred between species. Probabilistic models using the multispecies coalescent can be used in this framework for likelihood-based inference of both network topologies and parameters, including branch lengths and hybridization parameters. A difficulty for such methods is that it is not always clear whether, or to what extent, networks are identifiable-that is whether there could be two distinct networks that lead to the same distribution of gene trees. For cases in which incomplete lineage sorting occurs in addition to hybridization, we demonstrate a new representation of the species network likelihood that expresses the probability distribution of the gene tree topologies as a linear combination of gene tree distributions given a set of species trees. This representation makes it clear that in some cases in which two distinct networks give the same distribution of gene trees when sampling one allele per species, the two networks can be distinguished theoretically when multiple individuals are sampled per species. This result means that network identifiability is not only a function of the trees displayed by the networks but also depends on allele sampling within species. We additionally give an example in which two networks that display exactly the same trees can be distinguished from their gene trees even when there is only one lineage sampled per species. [gene tree, hybridization, identifiability, maximum likelihood, species tree, phylogeny.]., (© The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Classic null models for speciation and extinction give rise to phylogenies that differ in distribution from empirical phylogenies. In particular, empirical phylogenies are less balanced and have branching times closer to the root compared to phylogenies predicted by common null models. This difference might be due to null models of the speciation and extinction process being too simplistic, or due to the empirical datasets not being representative of random phylogenies. A third possibility arises because phylogenetic reconstruction methods often infer gene trees rather than species trees, producing an incongruity between models that predict species tree patterns and empirical analyses that consider gene trees. We investigate the extent to which the difference between gene trees and species trees under a combined birth-death and multispecies coalescent model can explain the difference in empirical trees and birth-death species trees. We simulate gene trees embedded in simulated species trees and investigate their difference with respect to tree balance and branching times. We observe that the gene trees are less balanced and typically have branching times closer to the root than the species trees. Empirical trees from TreeBase are also less balanced than our simulated species trees, and model gene trees can explain an imbalance increase of up to 8% compared to species trees. However, we see a much larger imbalance increase in empirical trees, about 100%, meaning that additional features must also be causing imbalance in empirical trees. This simulation study highlights the necessity of revisiting the assumptions made in phylogenetic analyses, as these assumptions, such as equating the gene tree with the species tree, might lead to a biased conclusion., (© The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.)

Species trees represent the historical divergences of populations or species, while gene trees trace the ancestry of individual gene copies sampled within those populations. In cases involving rapid speciation, gene trees with topologies that differ from that of the species tree can be most probable under the standard multispecies coalescent model, making species tree inference more difficult. Such anomalous gene trees are not well understood except for some small cases. In this work, we establish one constraint that applies to trees of any size: gene trees with "caterpillar" topologies cannot be anomalous. The proof of this involves a new combinatorial object, called a population history, which keeps track of the number of coalescent events in each ancestral population., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: There has been increasing interest in coalescent models which admit multiple mergers of ancestral lineages; and to model hybridization and coalescence simultaneously., Results: Hybrid-Lambda is a software package that simulates gene genealogies under multiple merger and Kingman's coalescent processes within species networks or species trees. Hybrid-Lambda allows different coalescent processes to be specified for different populations, and allows for time to be converted between generations and coalescent units, by specifying a population size for each population. In addition, Hybrid-Lambda can generate simulated datasets, assuming the infinitely many sites mutation model, and compute the F ST statistic. As an illustration, we apply Hybrid-Lambda to infer the time of subdivision of certain marine invertebrates under different coalescent processes., Conclusions: Hybrid-Lambda makes it possible to investigate biogeographic concordance among high fecundity species exhibiting skewed offspring distribution.

To infer species trees from gene trees estimated from phylogenomic data sets, tractable methods are needed that can handle dozens to hundreds of loci. We examine several computationally efficient approaches-MP-EST, STAR, STEAC, STELLS, and STEM-for inferring species trees from gene trees estimated using maximum likelihood (ML) and Bayesian approaches. Among the methods examined, we found that topology-based methods often performed better using ML gene trees and methods employing coalescent times typically performed better using Bayesian gene trees, with MP-EST, STAR, STEAC, and STELLS outperforming STEM under most conditions. We examine why the STEM tree (also called GLASS or Maximum Tree) is less accurate on estimated gene trees by comparing estimated and true coalescence times, performing species tree inference using simulations, and analyzing a great ape data set keeping track of false positive and false negative rates for inferred clades. We find that although true coalescence times are more ancient than speciation times under the multispecies coalescent model, estimated coalescence times are often more recent than speciation times. This underestimation can lead to increased bias and lack of resolution with increased sampling (either alleles or loci) when gene trees are estimated with ML. The problem appears to be less severe using Bayesian gene-tree estimates.

The coalescent and multispecies coalescent model rooted genealogies backward through time. Often, the direction of time is unknown in trees estimated from molecular sequences due to reversible mutation models, absence of an appropriate outgroup, and the absence of the molecular clock. In this article, probabilities of unrooted gene-tree topologies under the multispecies coalescent are considered. The main result is that for any species-tree topology with seven or more taxa, there exist branch lengths such that there are unrooted gene-tree topologies that are more likely than the one that has the same unrooted topology as the species tree. Species trees with such anomalous unrooted gene trees (AUGTs) are characterized for trees with five and six taxa, and patterns of branch lengths leading to AUGTs and rooted anomalous gene trees are explored. The results could be useful for understanding gene tree discordance and designing simulations studies for inferring challenging species trees.

Detailed calculations of the formation, guide, and mirror applied magnetic fields in the FRC compression-heating experiment (FRCHX) were conducted using a commercially available generalized finite element solver, COMSOL Multiphysics(®). In FRCHX, an applied magnetic field forms, translates, and finally captures the FRC in the liner region sufficiently long to enable compression. Large single turn coils generate the fast magnetic fields necessary for FRC formation. Solenoidal coils produce the magnetic field for translation and capture of the FRC prior to liner implosion. Due to the limited FRC lifetime, liner implosion is initiated before the FRC is injected, and the magnetic flux that diffuses into the liner is compressed. Two-dimensional axisymmetric magnetohydrodynamic simulations using MACH2 were used to specify optimal magnetic field characteristics, and this paper describes the simulations conducted to design magnetic field coils and compression hardware for FRCHX. This paper presents the vacuum solution for the magnetic field.

Many methods for inferring species trees from gene trees have been developed when incongruence among gene trees is due to incomplete lineage sorting. A method called STAR (Liu et al, 2009), assigns values to nodes in gene trees based only on topological information and uses the average value of the most recent common ancestor node for each pair of taxa to construct a distance matrix which is then used for clustering taxa into a tree. This method is very efficient computationally, scaling linearly in the number of loci and quadratically in the number of taxa, and in simulations has shown to be highly accurate for moderate to large numbers of loci as well as robust to molecular clock violations and misestimation of gene trees from sequence data. The method is based on a particular choice of numbering nodes in the gene trees; however, other choices for numbering nodes in gene trees can also lead to consistent inference of the species tree. Here, expected values and variances for average pairwise distances and differences between average pairwise distances in the distance matrix constructed by the STAR algorithm are used to analytically evaluate efficiency of different numbering schemes that are variations on the original STAR numbering for small trees.

The multispecies coalescent model describes the generation of gene trees from a rooted metric species tree and thus provides a framework for the inference of species trees from sampled gene trees. We prove that the STAR method of Liu et al. (2009) and generalizations of it, are statistically consistent methods of topological species tree inference under this model. We discuss the impact of gene tree sampling schemes for species tree inference using generalized STAR methods and reinterpret the original STAR as a consensus method based on clades.

Ranked gene trees, which consider both the gene tree topology and the sequence in which gene lineages separate, can potentially provide a new source of information for use in modeling genealogies and performing inference of species trees. Recently,we have calculated the probability distribution of ranked gene trees under the standard multispecies coalescent model for the evolution of gene lineages along the branches of a fixed species tree, demonstrating the existence of anomalous ranked gene trees (ARGTs), in which a ranked gene tree that does not match the ranked species tree can have greater probability under the model than the matching ranked gene tree. Here, we fully characterize the set of unranked species tree topologies that give rise to ARGTs, showing that this set contains all species tree topologies with five or more taxa, with the exceptions of caterpillars and pseudocaterpillars. The results have implications for the use of ranked gene trees in phylogenetic inference.

Probabilities of monophyly, paraphyly, and polyphyly of two-species gene genealogies are computed for modest sample sizes and compared for two different Λ coalescent processes. Coalescent processes belonging to the Λ coalescent family admit asynchronous multiple mergers of active ancestral lineages. Assigning a timescale to the time of divergence becomes a central issue when different populations have different coalescent processes running on different timescales. Clade probabilities in single populations are also computed, which can be useful for testing for taxonomic distinctiveness of an observed set of monophyletic lineages. The coalescence rates of multiple merger coalescent processes are functions of coalescent parameters. The effect of coalescent parameters on the probabilities studied depends on the coalescent process, and if the population is ancestral or derived. The probability of reciprocal monophyly tends to be somewhat lower, when associated with a Λ coalescent, under the null hypothesis that two groups come from the same population. However, even for fairly recent divergence times, the probability of monophyly tends to be higher as a function of the number of generations for coalescent processes that admit multiple mergers, and is sensitive to the parameter of one of the example processes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The ancestries of genes form gene trees which do not necessarily have the same topology as the species tree due to incomplete lineage sorting. Available algorithms determining the probability of a gene tree given a species tree require exponential computational runtime., Results: In this paper, we provide a polynomial time algorithm to calculate the probability of a ranked gene tree topology for a given species tree, where a ranked tree topology is a tree topology with the internal vertices being ordered. The probability of a gene tree topology can thus be calculated in polynomial time if the number of orderings of the internal vertices is a polynomial number. However, the complexity of calculating the probability of a gene tree topology with an exponential number of rankings for a given species tree remains unknown., Conclusions: Polynomial algorithms for calculating ranked gene tree probabilities may become useful in developing methodology to infer species trees based on a collection of gene trees, leading to a more accurate reconstruction of ancestral species relationships.

Purpose: The aim of the study was to ascertain whether a Cimino First policy can be implemented successfully in tertiary practice using a standardized technique., Methods: This is a retrospective study. All first radial-cephalic (Cimino) fistulas placed by a single surgeon in incident patients were studied. A standardized surgical technique was used paying attention to the dorsal cephalic branch. No balloon maturation or early surveillance was performed. Kaplan-Meier survival analysis using survfit function in R (Vienna) was applied., Results: Fifty-seven (69%) of 83 new accesses were radial cephalic fistulas. Of these, 44 (77.2%) were men. The patients were aged 17 to 83 (mean 54.1; SD 14.6) years. Whites comprised of 21 (36.8%), maori 18 (31.6%), and pacific islanders 16 (28.1%). Comorbidities included diabetes in 32 (56.1%), hypertension in 47 (82.5%), and hyperlipidemia in 25 (46.3%; n=54). Twenty-six (45.6%) were pre-dialysis. Mean body mass index was 30.74 (SD 6.9) Kg/m² (n=56). Mean vein diameter was 3.3 mm (range 2.1-6.2 mm; n=36). Twenty-six (45.6%) had had previous central lines. Forty-four (77.2%) fistulas matured. Mean maturation time was 14.0 weeks. Thirty-six (63.2%) were used for dialysis while eight patients remained pre-dialysis with patent fistulas. Primary patency at one year and 18 months was 69.2% and 57.4% respectively. The figures for assisted primary patency were 85.6% and 72.3% respectively. Secondary patency was 87.6% and 83.9% at one and two years., Conclusions: Cimino fistulas can be performed in a majority of patients with good results using a standardized surgical technique. The importance of the dorsal cephalic branch needs to be studied.

Gene tree topologies have proven a powerful data source for various tasks, including species tree inference and species delimitation. Consequently, methods for computing probabilities of gene trees within species trees have been developed and widely used in probabilistic inference frameworks. All these methods assume an underlying multispecies coalescent model. However, when reticulate evolutionary events such as hybridization occur, these methods are inadequate, as they do not account for such events. Methods that account for both hybridization and deep coalescence in computing the probability of a gene tree topology currently exist for very limited cases. However, no such methods exist for general cases, owing primarily to the fact that it is currently unknown how to compute the probability of a gene tree topology within the branches of a phylogenetic network. Here we present a novel method for computing the probability of gene tree topologies on phylogenetic networks and demonstrate its application to the inference of hybridization in the presence of incomplete lineage sorting. We reanalyze a Saccharomyces species data set for which multiple analyses had converged on a species tree candidate. Using our method, though, we show that an evolutionary hypothesis involving hybridization in this group has better support than one of strict divergence. A similar reanalysis on a group of three Drosophila species shows that the data is consistent with hybridization. Further, using extensive simulation studies, we demonstrate the power of gene tree topologies at obtaining accurate estimates of branch lengths and hybridization probabilities of a given phylogenetic network. Finally, we discuss identifiability issues with detecting hybridization, particularly in cases that involve extinction or incomplete sampling of taxa., Competing Interests: The authors have declared that no competing interests exist.

The properties of random gene tree topologies have recently been studied under a coalescent model that treats a species tree as a fixed parameter. Here we develop the analogous theory for random ranked gene tree topologies, in which both the topology and the sequence of coalescences for a random gene tree are considered. We derive the probability distribution of ranked gene tree topologies conditional on a fixed species tree. We then show that similar to the unranked case, ranked gene trees that do not match either the ranking or the topology of the species tree can have greater probability than the matching ranked gene tree., (Copyright © 2011 Elsevier Inc. All rights reserved.)

One approach to estimating a species tree from a collection of gene trees is to first estimate probabilities of clades from the gene trees, and then to construct the species tree from the estimated clade probabilities. While a greedy consensus algorithm, which consecutively accepts the most probable clades compatible with previously accepted clades, can be used for this second stage, this method is known to be statistically inconsistent under the multispecies coalescent model. This raises the question of whether it is theoretically possible to reconstruct the species tree from known probabilities of clades on gene trees. We investigate clade probabilities arising from the multispecies coalescent model, with an eye toward identifying features of the species tree. Clades on gene trees with probability greater than 1/3 are shown to reflect clades on the species tree, while those with smaller probabilities may not. Linear invariants of clade probabilities are studied both computationally and theoretically, with certain linear invariants giving insight into the clade structure of the species tree. For species trees with generic edge lengths, these invariants can be used to identify the species tree topology. These theoretical results both confirm that clade probabilities contain full information on the species tree topology and suggest future directions of study for developing statistically consistent inference methods from clade frequencies on gene trees., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Simulation studies have demonstrated that a variety of patterns in worldwide genetic variation are compatible with the trends predicted by a serial founder model, in which populations expand outward from an initial source via a process in which new populations contain only subsets of the genetic diversity present in their parental populations. Here, we provide analytical results for key quantities under the serial founder model, deriving distributions of coalescence times for pairs of lineages sampled either from the same population or from different populations. We use these distributions to obtain expectations for coalescence times and for homozygosity and heterozygosity values. A predicted approximate linear decline in expected heterozygosity with increasing distance from the source population reproduces a pattern that has been observed both in human genetic data and in simulations. Our formulas predict that populations close to the source location have lower between-population gene identity than populations far from the source, also mirroring results obtained from data and simulations. We show that different models that produce similar declining patterns in heterozygosity generate quite distinct patterns in coalescence-time distributions and gene identity measures, thereby providing a basis for distinguishing these models. We interpret the theoretical results in relation to their implications for human population genetics.

The Yule model and the coalescent model are two neutral stochastic models for generating trees in phylogenetics and population genetics, respectively. Although these models are quite different, they lead to identical distributions concerning the probability that pre-specified groups of taxa form monophyletic groups (clades) in the tree. We extend earlier work to derive exact formulae for the probability of finding one or more groups of taxa as clades in a rooted tree, or as 'clans' in an unrooted tree. Our findings are relevant for calculating the statistical significance of observed monophyly and reciprocal monophyly in phylogenetics., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Gene trees are evolutionary trees representing the ancestry of genes sampled from multiple populations. Species trees represent populations of individuals-each with many genes-splitting into new populations or species. The coalescent process, which models ancestry of gene copies within populations, is often used to model the probability distribution of gene trees given a fixed species tree. This multispecies coalescent model provides a framework for phylogeneticists to infer species trees from gene trees using maximum likelihood or Bayesian approaches. Because the coalescent models a branching process over time, all trees are typically assumed to be rooted in this setting. Often, however, gene trees inferred by traditional phylogenetic methods are unrooted. We investigate probabilities of unrooted gene trees under the multispecies coalescent model. We show that when there are four species with one gene sampled per species, the distribution of unrooted gene tree topologies identifies the unrooted species tree topology and some, but not all, information in the species tree edges (branch lengths). The location of the root on the species tree is not identifiable in this situation. However, for 5 or more species with one gene sampled per species, we show that the distribution of unrooted gene tree topologies identifies the rooted species tree topology and all its internal branch lengths. The length of any pendant branch leading to a leaf of the species tree is also identifiable for any species from which more than one gene is sampled.

Analyses of the increasingly available genomic data continue to reveal the extent of hybridization and its role in the evolutionary diversification of various groups of species. We show, through extensive coalescent-based simulations of multilocus data sets on phylogenetic networks, how divergence times before and after hybridization events can result in incomplete lineage sorting with gene tree incongruence signatures identical to those exhibited by hybridization. Evolutionary analysis of such data under the assumption of a species tree model can miss all hybridization events, whereas analysis under the assumption of a species network model would grossly overestimate hybridization events. These issues necessitate a paradigm shift in evolutionary analysis under these scenarios, from a model that assumes a priori a single source of gene tree incongruence to one that integrates multiple sources in a unifying framework. We propose a framework of coalescence within the branches of a phylogenetic network and show how this framework can be used to detect hybridization despite incomplete lineage sorting. We apply the model to simulated data and show that the signature of hybridization can be revealed as long as the interval between the divergence times of the species involved in hybridization is not too small. We reanalyze a data set of 106 loci from 7 in-group Saccharomyces species for which a species tree with no hybridization has been reported in the literature. Our analysis supports the hypothesis that hybridization occurred during the evolution of this group, explaining a large amount of the incongruence in the data. Our findings show that an integrative approach to gene tree incongruence and its reconciliation is needed. Our framework will help in systematically analyzing genomic data for the occurrence of hybridization and elucidating its evolutionary role.

Given a gene tree and a species tree, a coalescent history is a list of the branches of the species tree on which coalescences in the gene tree take place. Each pair consisting of a gene tree topology and a species tree topology has some number of possible coalescent histories. Here we show that, for each n>or=7, there exist a species tree topology S and a gene tree topology G not equalS, both with n leaves, for which the number of coalescent histories exceeds the corresponding number of coalescent histories when the species tree topology is S and the gene tree topology is also S. This result has the interpretation that the gene tree topology G discordant with the species tree topology S can be produced by the evolutionary process in more ways than can the gene tree topology that matches the species tree topology, providing further insight into the surprising combinatorial properties of gene trees that arise from their joint consideration with species trees.

Concatenated sequence alignments are often used to infer species-level relationships. Previous studies have shown that analysis of concatenated data using maximum likelihood (ML) can produce misleading results when loci have differing gene tree topologies due to incomplete lineage sorting. Here, we develop a polynomial time method that utilizes the modified mincut supertree algorithm to construct an estimated species tree from inferred rooted triples of concatenated alignments. We term this method SuperMatrix Rooted Triple (SMRT) and use the notation SMRT-ML when rooted triples are inferred by ML. We use simulations to investigate the performance of SMRT-ML under Jukes-Cantor and general time-reversible substitution models for four- and five-taxon species trees and also apply the method to an empirical data set of yeast genes. We find that SMRT-ML converges to the correct species tree in many cases in which ML on the full concatenated data set fails to do so. SMRT-ML can be conservative in that its output tree is often partially unresolved for problematic clades. We show analytically that when the species tree is clocklike and mutations occur under the Cavender-Farris-Neyman substitution model, as the number of genes increases, SMRT-ML is increasingly likely to infer the correct species tree even when the most likely gene tree does not match the species tree. SMRT-ML is therefore a computationally efficient and statistically consistent estimator of the species tree when gene trees are distributed according to the multispecies coalescent model.

Recent applications of principal components analysis (PCA) and multidimensional scaling (MDS) in human population genetics have found that "statistical maps" based on the genotypes in population-genetic samples often resemble geographic maps of the underlying sampling locations. To provide formal tests of these qualitative observations, we describe a Procrustes analysis approach for quantitatively assessing the similarity of population-genetic and geographic maps. We confirm in two scenarios, one using single-nucleotide polymorphism (SNP) data from Europe and one using SNP data worldwide, that a measurably high level of concordance exists between statistical maps of population-genetic variation and geographic maps of sampling locations. Two other examples illustrate the versatility of the Procrustes approach in population-genetic applications, verifying the concordance of SNP analyses using PCA and MDS, and showing that statistical maps of worldwide copy-number variants (CNVs) accord with statistical maps of SNP variation, especially when CNV analysis is limited to samples with the highest-quality data. As statistical maps with PCA and MDS have become increasingly common for use in summarizing population relationships, our examples highlight the potential of Procrustes-based quantitative comparisons for interpreting the results in these maps.

The field of phylogenetics is entering a new era in which trees of historical relationships between species are increasingly inferred from multilocus and genomic data. A major challenge for incorporating such large amounts of data into inference of species trees is that conflicting genealogical histories often exist in different genes throughout the genome. Recent advances in genealogical modeling suggest that resolving close species relationships is not quite as simple as applying more data to the problem. Here we discuss the complexities of genealogical discordance and review the issues that new methods for multilocus species tree inference will need to address to account successfully for naturally occurring genomic variability in evolutionary histories.

Consensus methods provide a useful strategy for summarizing information from a collection of gene trees. An important application of consensus methods is to combine gene trees to estimate a species tree. To investigate the theoretical properties of consensus trees that would be obtained from large numbers of loci evolving according to a basic evolutionary model, we construct consensus trees from rooted gene trees that occur in proportion to gene-tree probabilities derived from coalescent theory. We consider majority-rule, rooted triple (R(*)), and greedy consensus trees obtained from known, rooted gene trees, both in the asymptotic case as numbers of gene trees approach infinity and for finite numbers of genes. Our results show that for some combinations of species-tree branch lengths, increasing the number of independent loci can make the rooted majority-rule consensus tree more likely to be at least partially unresolved. However, the probability that the R(*) consensus tree has the species-tree topology approaches 1 as the number of gene trees approaches infinity. Although the greedy consensus algorithm can be the quickest to converge on the correct species-tree topology when increasing the number of gene trees, it can also be positively misleading. The majority-rule consensus tree is not a misleading estimator of the species-tree topology, and the R(*) consensus tree is a statistically consistent estimator of the species-tree topology. Our results therefore suggest a method for using multiple loci to infer the species-tree topology, even when it is discordant with the most likely gene tree.

Expression QTL mapping by integrating genome-wide gene expression and genotype data is a promising approach to identifying functional genetic variation, but is hampered by the large number of multiple comparisons inherent in such studies. A novel approach to addressing multiple testing problems in genome-wide family-based association studies is screening candidate markers using heritability or conditional power. We apply these methods in settings in which microarray gene expression data are used as phenotypes, screening for SNPs near the expressed genes. We perform association analyses for phenotypes using a univariate approach. We also perform simulations on trios with large numbers of causal SNPs to determine the optimal number of markers to use in a screen. We demonstrate that our family-based screening approach performs well in the analysis of integrative genomic datasets and that screening using either heritability or conditional power produces similar, though not identical, results.

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.

Background: Family-based association tests are important tools for investigating genetic risk factors of complex diseases. These tests are especially valuable for being robust to population structure. We introduce a tool, EFBAT, which performs exact family-based tests of association for X-chromosome and autosomal biallelic markers., Results: The program EFBAT extends a network algorithm previously applied to autosomal markers to include the X-chromosome and to perform tests of association under the null hypotheses "no association, no linkage" and "no association in the presence of linkage" under additive, dominant and recessive genetic models. These tests are valid regardless of patterns of missing familial data., Conclusion: The general framework for performing exact family-based association tests has been usefully extended to the X-chromosome, particularly for the hypothesis of "no association in the presence of linkage" and for different genetic models.

Although multiple gene sequences are becoming increasingly available for molecular phylogenetic inference, the analysis of such data has largely relied on inference methods designed for single genes. One of the common approaches to analyzing data from multiple genes is concatenation of the individual gene data to form a single supergene to which traditional phylogenetic inference procedures - e.g., maximum parsimony (MP) or maximum likelihood (ML) - are applied. Recent empirical studies have demonstrated that concatenation of sequences from multiple genes prior to phylogenetic analysis often results in inference of a single, well-supported phylogeny. Theoretical work, however, has shown that the coalescent can produce substantial variation in single-gene histories. Using simulation, we combine these ideas to examine the performance of the concatenation approach under conditions in which the coalescent produces a high level of discord among individual gene trees and show that it leads to statistically inconsistent estimation in this setting. Furthermore, use of the bootstrap to measure support for the inferred phylogeny can result in moderate to strong support for an incorrect tree under these conditions. These results highlight the importance of incorporating variation in gene histories into multilocus phylogenetics.

Because of the stochastic way in which lineages sort during speciation, gene trees may differ in topology from each other and from species trees. Surprisingly, assuming that genetic lineages follow a coalescent model of within-species evolution, we find that for any species tree topology with five or more species, there exist branch lengths for which gene tree discordance is so common that the most likely gene tree topology to evolve along the branches of a species tree differs from the species phylogeny. This counterintuitive result implies that in combining data on multiple loci, the straightforward procedure of using the most frequently observed gene tree topology as an estimate of the species tree topology can be asymptotically guaranteed to produce an incorrect estimate. We conclude with suggestions that can aid in overcoming this new obstacle to accurate genomic inference of species phylogenies., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Under the coalescent model for population divergence, lineage sorting can cause considerable variability in gene trees generated from any given species tree. In this paper, we derive a method for computing the distribution of gene tree topologies given a bifurcating species tree for trees with an arbitrary number of taxa in the case that there is one gene sampled per species. Applications for gene tree distributions include determining exact probabilities of topological equivalence between gene trees and species trees and inferring species trees from multiple datasets. In addition, we examine the shapes of gene tree distributions and their sensitivity to changes in branch lengths, species tree shape, and tree size. The method for computing gene tree distributions is implemented in the computer program COAL.

A fast ( approximately 300 ns), large-signal ( greater, similar1 V), free-standing foil bolometer was developed for measuring ultrasoft x-ray burst fluences. The results of bolometer measurements of the radiation output of an imploding foil liner plasma indicate yields of several tens of kJ, assuming isotropic emission. This is in substantial agreement with filtered metal photocathode (x-ray diode) measurements. The bolometer design, response function, and comparison with x-ray photodiode data are discussed. This type of bolometer is particularly applicable to radiation measurements of high-energy, destructive pulsed plasmas such as high-energy imploding liner plasmas.