The space of ultrametric phylogenetic trees

The reliability of a phylogenetic inference method from genomic sequence data is ensured by its statistical consistency. Bayesian inference methods produce a sample of phylogenetic trees from the posterior distribution given sequence data. Hence the question of statistical consistency of such methods is equivalent to the consistency of the summary of the sample. More generally, statistical consistency is ensured by the tree space used to analyse the sample. In this paper, we consider two standard parameterisations of phylogenetic time-trees used in evolutionary models: inter-coalescent interval lengths and absolute times of divergence events. For each of these parameterisations we introduce a natural metric space on ultrametric phylogenetic trees. We compare the introduced spaces with existing models of tree space and formulate several formal requirements that a metric space on phylogenetic trees must possess in order to be a satisfactory space for statistical analysis, and justify them. We show that only a few known constructions of the space of phylogenetic trees satisfy these requirements. However, our results suggest that these basic requirements are not enough to distinguish between the two metric spaces we introduce and that the choice between metric spaces requires additional properties to be considered. Particularly, that the summary tree minimising the square distance to the trees from the sample might be different for different parameterisations. This suggests that further fundamental insight is needed into the problem of statistical consistency of phylogenetic inference methods.Comment: Minor changes. This version has been published in JTB. 27 pages, 9 figure

Binding Phenomena Within A Reductionist Theory of Grammatical Dependencies

This thesis investigates the implications of binding phenomena for the development of a reductionist theory of grammatical dependencies. The starting point is the analysis of binding and control in Hornstein (2001, 2009). A number of revisions are made to this framework in order to develop a simpler and empirically more successful account of binding phenomena. The major development is the rejection of economy-based accounts of Condition B effects. It is argued that Condition B effects derive directly from an anti-locality constraint on A-movement. Competition between different dependency types is crucial to the analysis, but is formulated in terms of a heavily revised version of Reinhart's (2006) "No Sneaking" principle, rather than in terms of a simple economy preference for local over non-local dependencies. In contrast to Reinhart's No Sneaking, the condition presented here ("Keeping Up Appearances") has a phonologically rather than semantically specified comparison set. A key claim of the thesis is that the morphology of pronouns and reflexives is of little direct grammatical import. It is argued that much of the complexity of the contemporary binding literature derives from the attempt to capture the distribution of pronouns and reflexives in largely, or purely, syntactic and semantic terms. The analysis presented in this dissertation assigns a larger role to language-specific "spellout" rules, and to general pragmatic/interpretative principles governing the choice between competing morphemes. Thus, a core assumption of binding theory from LGB onwards is rejected: there is no syntactic theory which accounts for the distribution of pronouns and reflexives. Rather, there is a core theory of grammatical dependencies which must be conjoined with with phonological, morphological and pragmatic principles to yield the distributional facts in any given language. In this respect, the approach of the thesis is strictly non-lexicalist: there are no special lexical items which trigger certain kinds of grammatical dependency. All non-strictly-local grammatical dependencies are formed via A- or A-chains, and copies in these chains are pronounced according to a mix of universal principles and language-specific rules. The broader goal of the thesis is to further the prospects for a "reductionist" approach to grammatical dependencies along these lines. The most detailed empirical component of the thesis is an investigation of the problem posed by binding out of prepositional phrases. Even in a framework incorporating sideward movement, the apparent lack of c-command in this configuration poses a problem. Chapter 3 attempts to revive a variant of the traditional "reanalysis" account of binding out of PP. This segues into an investigation of certain properties of pseudopassivization and preposition stranding. The analyses in this thesis are stated within an informal syntactic framework. However, in order to investigate the precise implications of a particular economy condition, Merge over Move, a partial formalization of this framework is developed in chapter 4. This permits the economy condition to be stated precisely, and in a manner which does not have adverse implications for computational complexity

Efficient Bayesian inference under the structured coalescent

Motivation: Population structure significantly affects evolutionary dynamics. Such structure may be due to spatial segregation, but may also reflect any other gene-flow-limiting aspect of a model. In combination with the structured coalescent, this fact can be used to inform phylogenetic tree reconstruction, as well as to infer parameters such as migration rates and subpopulation sizes from annotated sequence data. However, conducting Bayesian inference under the structured coalescent is impeded by the difficulty of constructing Markov Chain Monte Carlo (MCMC) sampling algorithms (samplers) capable of efficiently exploring the state space. Results: In this article, we present a new MCMC sampler capable of sampling from posterior distributions over structured trees: timed phylogenetic trees in which lineages are associated with the distinct subpopulation in which they lie. The sampler includes a set of MCMC proposal functions that offer significant mixing improvements over a previously published method. Furthermore, its implementation as a BEAST 2 package ensures maximum flexibility with respect to model and prior specification. We demonstrate the usefulness of this new sampler by using it to infer migration rates and effective population sizes of H3N2 influenza between New Zealand, New York and Hong Kong from publicly available hemagglutinin (HA) gene sequences under the structured coalescent. Availability and implementation: The sampler has been implemented as a publicly available BEAST 2 package that is distributed under version 3 of the GNU General Public License at http://compevol.github.io/MultiTypeTree. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

A case of intercommunity lethal aggression by chimpanzees in an open and dry landscape, Issa Valley, western Tanzania

Intercommunity (lethal) aggression is a familiar component of the behavioural repertoire of many forest-dwelling chimpanzee (Pan troglodytes) communities. However, until now, the absence of intercommunity attacks - including killings - in communities that live in open, mosaic environments has supported hypotheses of reduced resource competition in drier habitats, and informed referential models of early hominin social dynamics in a similar habitat. In June 2020, we observed the first instance of intercommunity lethal aggression, a male-committed infanticide, by the Issa chimpanzee community, which live in a savannah-mosaic habitat in the Issa Valley, western Tanzania. The carcass was recovered by researchers after it was abandoned by the attackers. Here, we give a detailed account of the events leading up to and including the infanticide, and contextualise our observations with what has been described for other chimpanzee communities. Notably, in contrast to the majority of reported intercommunity infanticides, the infant male victim was castrated (and not cannibalised), making this the youngest reported castration. This observation of intercommunity aggression disproves its hypothesised absence in savannah-dwelling chimpanzees, which by extension, has implications for early hominin evolution. We suggest that the near absence of observations of intercommunity aggression in savannah chimpanzee communities is most likely due to the lack of long-term study communities, and in some cases geographic isolation. We hypothesise that food-rich areas within a habitat with otherwise widely distributed food sources may select for intense intercommunity aggression despite the low population density characteristic of savannah communities. Anecdotes such as this add to the comparative database available on intercommunity killings in chimpanzee society, improving our ability to draw inferences about their evolutionary significance

Visual Function Questionnaire as an outcome measure for homonymous hemianopia: subscales and supplementary questions, analysis from the VISION trial

Background: We conduct supplementary analyses of the NEI VFQ-25 data to evaluate where changes occurred within subscales of the NEI VFQ-25 leading to change in the composite scores between the three treatment arms, and evaluate the NEI VFQ-25 with and without the Neuro 10 supplement. Methods: A prospective, multicentre, parallel, single-blind, three-arm RCT of fourteen UK acute stroke units was conducted. Stroke survivors with homonymous hemianopia were recruited. Interventions included: Fresnel prisms for minimum 2 h, 5 days/week over 6-weeks (Arm a), Visual search training for minimum 30 min, 5 days/week over 6-weeks (Arm b) and standard care-information only (Arm c). Primary and secondary outcomes (including NEI VFQ-25 data) were measured at baseline, 6, 12 and 26 weeks after randomisation. Results: Eighty seven patients were recruited (69% male; mean age (SD) equal to 69 (12) years). At 26 weeks, outcomes for 24, 24 and 22 patients, respectively, were compared to baseline. NEI VFQ-25 (with and without Neuro 10) responses improved from baseline to 26 weeks with visual search training compared to Fresnel prisms and standard care. In subscale analysis, the most impacted across all treatment arms was ‘driving’ whilst the least impacted were ‘colour vision’ and ‘ocular pain’. Conclusions: Composite scores differed systematically for the NEI VFQ-25 (Neuro 10) versus NEI VFQ-25 at all time points. For subscale scores, descriptive statistics suggest clinically relevant improvement in distance activities and vision-specific dependency subscales for NEI VFQ-25 scores in the visual search treatment arm. Trial Registration: Current Controlled Trials ISRCTN05956042

Wild chimpanzee behavior suggests that a savanna-mosaic habitat did not support the emergence of hominin terrestrial bipedalism

Bipedalism, a defining feature of the human lineage, is thought to have evolved as forests retreated in the late Miocene-Pliocene. Chimpanzees living in analogous habitats to early hominins offer a unique opportunity to investigate the ecological drivers of bipedalism that cannot be addressed via the fossil record alone. We investigated positional behavior and terrestriality in a savanna-mosaic community of chimpanzees (Pan troglodytes schweinfurthii) in the Issa Valley, Tanzania as the first test in a living ape of the hypothesis that wooded, savanna habitats were a catalyst for terrestrial bipedalism. Contrary to widely accepted hypotheses of increased terrestriality selecting for habitual bipedalism, results indicate that trees remained an essential component of the hominin adaptive niche, with bipedalism evolving in an arboreal context, likely driven by foraging strategy

Accounting for errors in data improves divergence time estimates in single-cell cancer evolution

Single-cell sequencing provides a new way to explore the evolutionary history of cells. Compared to traditional bulk sequencing, where a population of heterogeneous cells is pooled to form a single observation, single-cell sequencing isolates and amplifies genetic material from individual cells, thereby preserving the information about the origin of the sequences. However, single-cell data is more error-prone than bulk sequencing data due to the limited genomic material available per cell. Here, we present error and mutation models for evolutionary inference of single-cell data within a mature and extensible Bayesian framework, BEAST2. Our framework enables integration with biologically informative models such as relaxed molecular clocks and population dynamic models. Our simulations show that modeling errors increase the accuracy of relative divergence times and substitution parameters. We reconstruct the phylogenetic history of a colorectal cancer patient and a healthy patient from single-cell DNA sequencing data. We find that the estimated times of terminal splitting events are shifted forward in time compared to models which ignore errors. We observed that not accounting for errors can overestimate the phylogenetic diversity in single-cell DNA sequencing data. We estimate that 30-50% of the apparent diversity can be attributed to error. Our work enables a full Bayesian approach capable of accounting for errors in the data within the integrative Bayesian software framework BEAST2

Pragmatic randomised controlled trial to evaluate the effectiveness and cost effectiveness of a multi-component intervention to reduce substance use and risk-taking behaviour in adolescents involved in the criminal justice system: A trial protocol (RISKIT-CJS)

Background: Adolescence is a critical developmental stage when young people make lifestyle choices that have the potential to impact on their current and future health and social wellbeing. The relationship between substance use and criminal activity is complex but there is clear evidence that the prevalence of problematic substance use is far higher among adolescent offenders than the general adolescent population. Adolescent offenders are a marginalized and vulnerable population who are significantly more likely to experience health and social inequalities in later life than their non-offending peers. There is a paucity of evidence on effective interventions to address substance use and risk-taking behaviours in adolescent offender populations but it is clear that preventative or abstinence orientated interventions are not effective. RISKIT-CJS is an intervention developed in collaboration with young people taking account of the current best evidence. Feasibility and pilot studies have found the intervention addresses the needs of adolescents, is acceptable and has demonstrated potential in reducing substance use and risk-taking behavior. Methods: The study is a mixed method, two-armed, prospective, pragmatic randomized controlled trial with individual randomisation to either treatment as usual alone or the RISKIT-CJS intervention in addition to treatment as usual. Adolescents, aged 13 to 17 years inclusive, engaged with the criminal justice system who are identified as having problematic substance use are eligible to participate. The study will be conducted across three geographical areas; South and South East England, London and North East England between March 2017 and February 2019. Discussion: The study represents an ambitious programme of work to address an area of need for a marginalized and vulnerable population