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Poon A.F.Y.,Center for Excellence in AIDS | Poon A.F.Y.,University of British Columbia | Poon A.F.Y.,Simon Fraser University
Molecular Biology and Evolution | Year: 2015

The shapes of phylogenetic trees relating virus populations are determined by the adaptation of viruses within each host, and by the transmission of viruses among hosts. Phylodynamic inference attempts to reverse this flow of information, estimating parameters of these processes from the shape of a virus phylogeny reconstructed from a sample of genetic sequences from the epidemic. A key challenge to phylodynamic inference is quantifying the similarity between two trees in an efficient and comprehensive way. In this study, I demonstrate that a new distance measure, based on a subset tree kernel function from computational linguistics, confers a significant improvement over previous measures of tree shape for classifying trees generated under different epidemiological scenarios. Next, I incorporate this kernel-based distance measure into an approximate Bayesian computation (ABC) framework for phylodynamic inference. ABC bypasses the need for an analytical solution of model likelihood, as it only requires the ability to simulate data from the model. I validate this "kernel-ABC" method for phylodynamic inference by estimating parameters from data simulated under a simple epidemiological model. Results indicate that kernel-ABC attained greater accuracy for parameters associated with virus transmission than leading software on the same data sets. Finally, I apply the kernel-ABC framework to study a recent outbreak of a recombinant HIV subtype in China. Kernel-ABC provides a versatile framework for phylodynamic inference because it can fit a broader range of models than methods that rely on the computation of exact likelihoods. © 2015 The Author. Source


Jetz W.,Yale University | Jetz W.,Imperial College London | Thomas G.H.,University of Sheffield | Joy J.B.,Yale University | And 5 more authors.
Current Biology | Year: 2014

Background Integrated, efficient, and global prioritization approaches are necessary to manage the ongoing loss of species and their associated function. "Evolutionary distinctness" measures a species' contribution to the total evolutionary history of its clade and is expected to capture uniquely divergent genomes and functions. Here we demonstrate how such a metric identifies species and regions of particular value for safeguarding evolutionary diversity. Results Among the world's 9,993 recognized bird species, evolutionary distinctness is very heterogeneously distributed on the phylogenetic tree and varies little with range size or threat level. Species representing the most evolutionary history over the smallest area (those with greatest "evolutionary distinctness rarity") as well as some of the most imperiled distinct species are often concentrated outside the species-rich regions and countries, suggesting they may not be well captured by current conservation planning. We perform global cross-species and spatial analyses and generate minimum conservation sets to assess the benefits of the presented species-level metrics. We find that prioritizing imperiled species by their evolutionary distinctness and geographic rarity is a surprisingly effective and spatially economical way to maintain the total evolutionary information encompassing the world's birds. We identify potential conservation gaps in relation to the existing reserve network that in particular highlight islands as effective priority areas. Conclusions The presented distinctness metrics are effective yet easily communicable and versatile tools to assist objective global conservation decision making. Given that most species will remain ecologically understudied, combining growing phylogenetic and spatial data may be an efficient way to retain vital aspects of biodiversity. © 2014 The Authors. Source


Pakula B.,University of British Columbia | Shoveller J.,University of British Columbia | Shoveller J.,Center for Excellence in AIDS | Ratner P.A.,University of British Columbia | Carpiano R.,University of British Columbia
American Journal of Public Health | Year: 2016

Objectives. To investigate the prevalence and co-occurrence of heavy drinking, anxiety, and Mood disorders among Canadians who self-identified as gay, lesbian, bisexual, or heterosexual. Methods. Pooled data from the 2007 to 2012 cycles of the Canadian Community Health Survey (n = 222 548) were used to fit logistic regression models controlling for sociodemographic characteristics. Results. In adjusted logistic regression models, gay or lesbian respondents had greater odds than heterosexual respondents of reporting anxiety disorders, mood disorders, and anxiety-mood disorders. Bisexual respondents had greater odds of reporting anxiety disorders, mood disorders, anxiety-mood disorders, and heavy drinking. Gay or lesbian and bisexual respondents had greater odds than heterosexuals of reporting co-occurring anxiety or mood disorders and heavy drinking. The highest rates of disorders were observed among bisexual respondents, with nearly quadruple the rates of anxiety, mood, and combined anxiety and mood disorders relative to heterosexuals and approximately twice the rates of gay or lesbian respondents. Conclusions. Members of sexual minority groups in Canada, in particular those self identifying as bisexual, experience disproportionate rates of anxiety and mood disorders, heavy drinking, and co-occurring disorders. Source


Werb D.,Center for Excellence in AIDS | Buxton J.,Center for Disease Control | Shoveller J.,University of British Columbia | Richardson C.,University of British Columbia | And 2 more authors.
Drug and Alcohol Dependence | Year: 2013

Background: Injection drug use has been identified as a key source of morbidity and mortality, primarily from overdose and the transmission of blood-borne diseases such as HIV. Experts have therefore called for the prioritization of resources toward the prevention of injection drug use. However, these strategies have not been systematically assessed. Methods: PRISMA guidelines were used to systematically review and extract findings from the peer-reviewed literature evaluating the effectiveness of interventions to prevent injecting initiation. We searched 10 English language electronic databases (PubMed, PsycINFO, EMBASE, Cochrane CENTRAL, CINAHL, Web of Science, TOXNET, AIDSLINE, AMED and ERIC), the Internet (Google, Google Scholar), and article reference lists, from database inception to June 1st, 2012. Results: Overall, out of 384 studies identified in the initial search, eight met the inclusion criteria. Studies evaluated four different types of interventions: social marketing, peer-based behavior modification, treatment, and drug law enforcement. Four studies observed a significant effect of the intervention on reducing rates of injecting initiation. Peer-based behavior modification and addiction treatment interventions were found to be most effective. Two of three studies assessing the impact of drug law enforcement on patterns of injecting initiation found no impact on injecting initiation, while one study reported inconclusive results. Conclusion: There exists a limited scientific literature on strategies to prevent injecting initiation. Resources should be allocated toward increased research and development of effective interventions to prevent this phenomenon. © 2013 Elsevier Ireland Ltd. Source


Sluis-Cremer N.,University of Pittsburgh | Huber K.D.,University of Pittsburgh | Brumme C.J.,Center for Excellence in AIDS | Brumme C.J.,University of British Columbia | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

We characterized the relative fitness of multiple nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistant HIV-1 variants in the presence of etravirine (ETV), rilpivirine (RPV), and/or the nucleoside RT inhibitor emtricitabine (FTC) by simultaneous competitive culture and 454 deep sequencing. The E138A substitution, typically associated with decreased virologic responses to ETV- and RPV-containing regimens, confers a clear fitness advantage to the virus in the presence of FTC and decreases FTC susceptibility 4.7-fold. Copyright © 2014, American Society for Microbiology. All Rights Reserved. Source

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