Publications by authors named "Michael Douglas"

124 Publications

Taxonomic Uncertainty and the Anomaly Zone: Phylogenomics Disentangle a Rapid Radiation to Resolve Contentious Species (Gila robusta complex) in the Colorado River.

Genome Biol Evol 2021 Aug 25. Epub 2021 Aug 25.

Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas 72701, USA.

Species are indisputable units for biodiversity conservation, yet their delimitation is fraught with both conceptual and methodological difficulties. A classic example is the taxonomic controversy surrounding the Gila robusta complex in the lower Colorado River of southwestern North America. Nominal species designations were originally defined according to weakly diagnostic morphological differences, but these conflicted with subsequent genetic analyses. Given this ambiguity, the complex was re-defined as a single polytypic unit, with the proposed 'threatened' status under the U.S. Endangered Species Act of two elements being withdrawn. Here we re-evaluated the status of the complex by utilizing dense spatial and genomic sampling (N = 387 and >22k loci), coupled with SNP-based coalescent and polymorphism-aware phylogenetic models. In doing so, we found that all three species were indeed supported as evolutionarily independent lineages, despite widespread phylogenetic discordance. To juxtapose this discrepancy with previous studies, we first categorized those evolutionary mechanisms driving discordance, then tested (and subsequently rejected) prior hypotheses which argued phylogenetic discord in the complex was driven by the hybrid origin of Gila nigra. The inconsistent patterns of diversity we found within G. robusta were instead associated with rapid Plio-Pleistocene drainage evolution, with subsequent divergence within the 'anomaly zone' of tree space producing ambiguities that served to confound prior studies. Our results not only support resurrection of the three species as distinct entities, but also offer an empirical example of how phylogenetic discordance can be categorized within other recalcitrant taxa, particularly when variation is primarily partitioned at the species-level.
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http://dx.doi.org/10.1093/gbe/evab200DOI Listing
August 2021

Born to move: a review on the impact of physical exercise on brain health and the evidence from human controlled trials.

Arq Neuropsiquiatr 2021 06;79(6):536-550

Universidade Tiradentes, Departamento de Medicina, Laboratório de Biociências da Cinética Humana, Aracaju SE, Brazil.

Background: Physical exercise has been found to impact neurophysiological and structural aspects of the human brain. However, most research has used animal models, which yields much confusion regarding the real effects of exercise on the human brain, as well as the underlying mechanisms.

Objective: To present an update on the impact of physical exercise on brain health; and to review and analyze the evidence exclusively from human randomized controlled studies from the last six years.

Methods: A search of the literature search was conducted using the MEDLINE (via PubMed), EMBASE, Web of Science and PsycINFO databases for all randomized controlled trials published between January 2014 and January 2020.

Results: Twenty-four human controlled trials that observed the relationship between exercise and structural or neurochemical changes were reviewed.

Conclusions: Even though this review found that physical exercise improves brain plasticity in humans, particularly through changes in brain-derived neurotrophic factor (BDNF), functional connectivity, basal ganglia and the hippocampus, many unanswered questions remain. Given the recent advances on this subject and its therapeutic potential for the general population, it is hoped that this review and future research correlating molecular, psychological and image data may help elucidate the mechanisms through which physical exercise improves brain health.
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http://dx.doi.org/10.1590/0004-282X-ANP-2020-0166DOI Listing
June 2021

Influence of payer coverage and out-of-pocket costs on ordering of NGS panel tests for hereditary cancer in diverse settings.

J Genet Couns 2021 Jul 7. Epub 2021 Jul 7.

Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, CA, USA.

The landscape of payment for genetic testing has been changing, with an increase in the number of laboratories offering testing, larger panel offerings, and lower prices. To determine the influence of payer coverage and out-of-pocket costs on the ordering of NGS panel tests for hereditary cancer in diverse settings, we conducted semi-structured interviews with providers who conduct genetic counseling and order next-generation sequencing (NGS) panels purposefully recruited from 11 safety-net clinics and academic medical centers (AMCs) in California and North Carolina, states with diverse populations and divergent Medicaid expansion policies. Thematic analysis was done to identify themes related to the impact of reimbursement and out-of-pocket expenses on test ordering. Specific focus was put on differences between settings. Respondents from both safety-net clinics and AMCs reported that they are increasingly ordering panels instead of single-gene tests, and tests were ordered primarily from a few commercial laboratories. Surprisingly, safety-net clinics reported few barriers to testing related to cost, largely due to laboratory assistance with prior authorization requests and patient payment assistance programs that result in little to no patient out-of-pocket expenses. AMCs reported greater challenges navigating insurance issues, particularly prior authorization. Both groups cited non-coverage of genetic counseling as a major barrier to testing. Difficulty of access to cascade testing, particularly for family members that do not live in the United States, was also of concern. Long-term sustainability of laboratory payment assistance programs was a major concern; safety-net clinics were particularly concerned about access to testing without such programs. There were few differences between states. In conclusion, the use of laboratories with payment assistance programs reduces barriers to NGS panel testing among diverse populations. Such programs represent a major change to the financing and affordability of genetic testing. However, access to genetic counseling is a barrier and must be addressed to ensure equity in testing.
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http://dx.doi.org/10.1002/jgc4.1459DOI Listing
July 2021

Spatial population genetics in heavily managed species: Separating patterns of historical translocation from contemporary gene flow in white-tailed deer.

Evol Appl 2021 Jun 4;14(6):1673-1689. Epub 2021 May 4.

Department of Biological Sciences University of Arkansas Fayetteville AR USA.

Approximately 100 years ago, unregulated harvest nearly eliminated white-tailed deer () from eastern North America, which subsequently served to catalyze wildlife management as a national priority. An extensive stock-replenishment effort soon followed, with deer broadly translocated among states as a means of re-establishment. However, an unintended consequence was that natural patterns of gene flow became obscured and pretranslocation signatures of population structure were replaced. We applied cutting-edge molecular and biogeographic tools to disentangle genetic signatures of historical management from those reflecting spatially heterogeneous dispersal by evaluating 35,099 single nucleotide polymorphisms (SNPs) derived via reduced-representation genomic sequencing from 1143 deer sampled statewide in Arkansas. We then employed Simpson's diversity index to summarize ancestry assignments and visualize spatial genetic transitions. Using sub-sampled transects across these transitions, we tested clinal patterns across loci against theoretical expectations of their response under scenarios of re-colonization and restricted dispersal. Two salient results emerged: (A) Genetic signatures from historic translocations are demonstrably apparent; and (B) Geographic filters (major rivers; urban centers; highways) now act as inflection points for the distribution of this contemporary ancestry. These results yielded a statewide assessment of contemporary population structure in deer as driven by historic translocations as well as ongoing processes. In addition, the analytical framework employed herein to effectively decipher extant/historic drivers of deer distribution in Arkansas is also applicable for other biodiversity elements with similarly complex demographic histories.
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http://dx.doi.org/10.1111/eva.13233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210790PMC
June 2021

Impacts of detritivore diversity loss on instream decomposition are greatest in the tropics.

Nat Commun 2021 06 17;12(1):3700. Epub 2021 Jun 17.

Facultad de Ciencias Ambientales y Centro EULA-Chile, Universidad de Concepción, Concepción, Chile.

The relationship between detritivore diversity and decomposition can provide information on how biogeochemical cycles are affected by ongoing rates of extinction, but such evidence has come mostly from local studies and microcosm experiments. We conducted a globally distributed experiment (38 streams across 23 countries in 6 continents) using standardised methods to test the hypothesis that detritivore diversity enhances litter decomposition in streams, to establish the role of other characteristics of detritivore assemblages (abundance, biomass and body size), and to determine how patterns vary across realms, biomes and climates. We observed a positive relationship between diversity and decomposition, strongest in tropical areas, and a key role of abundance and biomass at higher latitudes. Our results suggest that litter decomposition might be altered by detritivore extinctions, particularly in tropical areas, where detritivore diversity is already relatively low and some environmental stressors particularly prevalent.
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http://dx.doi.org/10.1038/s41467-021-23930-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211652PMC
June 2021

Teaching Vocabulary to Improve Print Knowledge in Preschool Children with Hearing Loss.

Perspect ASHA Spec Interest Groups 2020 Dec 17;5(6):1366-1379. Epub 2020 Aug 17.

Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC.

Purpose: The purpose of this article was to examine evidence that (a) published measures may tap different categories of print knowledge and result in disparate findings in the literature, (b) concept vocabulary knowledge in children with hearing loss may exacerbate deficits in conceptual print knowledge, and (c) concept vocabulary can be taught via direct instruction for preschool children with hearing loss.

Method: In Study 1, an item analysis of published print knowledge measures was performed to determine the prevalence of concept vocabulary in test items. Additionally, the performance on a conceptual print knowledge measure was compared for preschool children with and without hearing loss. In Study 2, four preschool children participated in a multiple probe across behaviors treatment design to determine if concept vocabulary could be explicitly taught to children with hearing loss.

Results: Differences emerged in use of concept vocabulary on test items across the measures, which may explain disparate findings that have been reported in this area. Additionally, children with hearing loss performed lower than children with typical hearing on items that contained concept vocabulary but not on items that did not. Finally, we found initial evidence that direct instruction can improve concept vocabulary for children with hearing loss, and it might not be necessary to separately target each concept category.

Conclusion: This series of studies lays groundwork for future research confirming a connection between conceptual print knowledge and conceptual vocabulary knowledge, and offers evidence for intervention that could be used clinically to teach conceptual vocabulary.
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http://dx.doi.org/10.1044/2020_persp-20-00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112279PMC
December 2020

Laboratory business models and practices: implications for availability and access to germline genetic testing.

Genet Med 2021 May 6. Epub 2021 May 6.

Center for Translational and Policy Research on Personalized Medicine (TRANSPERS), Department of Clinical Pharmacy, University of California-San Francisco, San Francisco, CA, USA.

Purpose: Germline testing laboratories have evolved over several decades. We describe laboratory business models and practices and explore their implications on germline testing availability and access.

Methods: We conducted semistructured interviews with key informants using purposive sampling. We interviewed 13 key informants representing 14 laboratories. We used triangulation and iterative data analysis to identify topics concerning laboratory business models and practices.

Results: We characterized laboratories as full-service (FSL), for-profit germline (PGL), and not-for-profit germline (NGL). Relying on existing payer contracts is a key characteristic of the FSL business models. FSLs focus on high-volume germline tests with evidence of clinical utility that have reimbursable codes. In comparison, a key business model characteristic of PGLs is direct patient billing facilitated by commodity-based pricing made possible by investors and industry partnerships. Client billing is a key business model characteristic of NGLs. Because many NGLs exist within academic settings, they are challenged by their inability to optimize laboratory processes and billing practices.

Conclusion: Continued availability of, and access to germline testing will depend on the financial success of laboratories; organizational characteristics of laboratories and payers; cultural factors, particularly consumer interest and trust; and societal factors, such as regulation and laws surrounding pricing and reimbursement.
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http://dx.doi.org/10.1038/s41436-021-01184-zDOI Listing
May 2021

Latitude dictates plant diversity effects on instream decomposition.

Sci Adv 2021 Mar 26;7(13). Epub 2021 Mar 26.

Marine Institute, Furnace, Newport, Ireland.

Running waters contribute substantially to global carbon fluxes through decomposition of terrestrial plant litter by aquatic microorganisms and detritivores. Diversity of this litter may influence instream decomposition globally in ways that are not yet understood. We investigated latitudinal differences in decomposition of litter mixtures of low and high functional diversity in 40 streams on 6 continents and spanning 113° of latitude. Despite important variability in our dataset, we found latitudinal differences in the effect of litter functional diversity on decomposition, which we explained as evolutionary adaptations of litter-consuming detritivores to resource availability. Specifically, a balanced diet effect appears to operate at lower latitudes versus a resource concentration effect at higher latitudes. The latitudinal pattern indicates that loss of plant functional diversity will have different consequences on carbon fluxes across the globe, with greater repercussions likely at low latitudes.
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http://dx.doi.org/10.1126/sciadv.abe7860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997509PMC
March 2021

Availability and funding of clinical genomic sequencing globally.

BMJ Glob Health 2021 02;6(2)

Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

The emergence of next-generation genomic sequencing (NGS) tests for use in clinical care has generated widespread interest around the globe, but little is known about the availability and funding of these tests worldwide. We examined NGS availability across world regions and countries, with a particular focus on availability of three key NGS tests-Whole-Exome Sequencing or Whole-Genome Sequencing for diagnosis of suspected genetic diseases such as intellectual disability disorders or rare diseases, non-invasive prenatal testing for common genetic abnormalities in fetuses and tumor sequencing for therapy selection and monitoring of cancer treatment. We found that these NGS tests are available or becoming available in every major region of the world. This includes both high-income countries with robust genomic programmes such as the USA and the UK, and growing availability in countries with upper-middle-income economies. We used exploratory case studies across three diverse health care systems (publicly funded/national (UK), publicly funded/provincial (Canada) and mixed private/public system (USA)) to illustrate the funding challenges and approaches used to address those challenges that might be adopted by other countries. We conclude by assessing what type of data and initiatives will be needed to better track and understand the use of NGS around the world as such testing continues to expand.
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http://dx.doi.org/10.1136/bmjgh-2020-004415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880109PMC
February 2021

The choices we make and the impacts they have: Machine learning and species delimitation in North American box turtles (Terrapene spp.).

Mol Ecol Resour 2021 Feb 10. Epub 2021 Feb 10.

Department of Biological Sciences, University of Arkansas, Fayetteville, AR, USA.

Model-based approaches that attempt to delimit species are hampered by computational limitations as well as the unfortunate tendency by users to disregard algorithmic assumptions. Alternatives are clearly needed, and machine-learning (M-L) is attractive in this regard as it functions without the need to explicitly define a species concept. Unfortunately, its performance will vary according to which (of several) bioinformatic parameters are invoked. Herein, we gauge the effectiveness of M-L-based species-delimitation algorithms by parsing 64 variably-filtered versions of a ddRAD-derived SNP data set collected from North American box turtles (Terrapene spp.). Our filtering strategies included: (i) minor allele frequencies (MAF) of 5%, 3%, 1%, and 0% (= none), and (ii) maximum missing data per-individual/per-population at 25%, 50%, 75%, and 100% (= no filtering). We found that species-delimitation via unsupervised M-L impacted the signal-to-noise ratio in our data, as well as the discordance among resolved clades. The latter may also reflect biogeographic history, gene flow, incomplete lineage sorting, or combinations thereof (as corroborated from previously observed patterns of differential introgression). Our results substantiate M-L as a viable species-delimitation method, but also demonstrate how commonly observed patterns of phylogenetic discordance can seriously impact M-L-classification.
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http://dx.doi.org/10.1111/1755-0998.13350DOI Listing
February 2021

Private payer coverage policies for ApoE-e4 genetic testing.

Genet Med 2021 04 8;23(4):614-620. Epub 2021 Jan 8.

Center for Translational and Policy Research on Personalized Medicine (TRANSPERS), University of California, San Francisco, San Francisco, CA, USA.

Purpose: ApoE-e4 has a well-established connection to late-onset Alzheimer disease (AD) and is available clinically. Yet, there have been no analyses of payer coverage policies for ApoE. Our objective was to analyze private payer coverage policies for ApoE genetic testing, examine the rationales, and describe supporting evidence referenced by policies.

Methods: We searched for policies from the eight largest private payers (by member numbers) covering ApoE testing for late-onset AD. We implemented content analysis methods to evaluate policies for coverage decisions and rationales.

Results: Seven payers had policies with positions on ApoE testing. Five explicitly state they do not cover ApoE and two apply generic preauthorization criteria. Rationales supporting coverage decisions include: reference to guidelines or national standards, inadequate data supporting testing, characterizing testing as investigational, or that testing would not alter patients' clinical management.

Conclusion: Seven of the eight largest private payers' coverage policies reflect standards that discourage ApoE testing due to a lack of clinical utility. As the field advances, ApoE testing may have an important clinical role, particularly considering that disease-modifying therapies are under evaluation by the US Food and Drug Administration. These types of field advancements may not be consistent with private payers' policies and may cause payers to reevaluate existing coverage policies.
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http://dx.doi.org/10.1038/s41436-020-01042-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035237PMC
April 2021

Fatigue and fluctuations in physical and psychological wellbeing in people with multiple sclerosis: A longitudinal study.

Mult Scler Relat Disord 2021 Jan 24;47:102602. Epub 2020 Oct 24.

Physical Activity and Well-Being Research Group, School of Psychology, Curtin University, Western Australia, Australia.

Background: Fatigue is a highly prevalent and disabling symptom of multiple sclerosis (MS). The aetiology remains unclear, potentially resulting from neuroinflammatory or neurodegenerative processes, mood disturbance, MS symptoms including pain, poor sleep, physical decompensation or medication side effects. Cross-sectional associations have been reported between fatigue and markers of physical and psychological health in people with MS. The current study examined if fluctuations in markers of physical and psychological wellbeing were associated with between-person differences in fatigue in MS.

Methods: Longitudinal data of up to 7 years was available of 3369 people with MS who were enrolled in the UK MS Register. Participants completed MS impact scale ratings and MS walking scales up to 4 times per year for up to 7 years. Fatigue was assessed at one time point using the Fatigue Severity Scale. Multilevel analyses were conducted to examine the degree of variance in the outcome measures accounted for by fatigue.

Results: Fatigue was associated with fluctuations in depression, MS impact, and walking ability, and to a lesser extent with fluctuations in anxiety and perceived health status. Interference of fatigue in participation in social activities and work-related responsibilities and the physical effects of fatigue were most strongly related to MS-related outcomes.

Conclusion: Given the strong associations between fatigue and many MS outcomes, fatigue management interventions are likely to impact on different aspects of physical and psychological wellbeing in MS.
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http://dx.doi.org/10.1016/j.msard.2020.102602DOI Listing
January 2021

Expanding Use of Clinical Genome Sequencing and the Need for More Data on Implementation.

JAMA 2020 11;324(20):2029-2030

Cumming School of Medicine, Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1001/jama.2020.19933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686292PMC
November 2020

Age structuring and spatial heterogeneity in prion protein gene () polymorphism in white-tailed deer.

Prion 2020 12;14(1):238-248

Department of Biological Sciences, University of Arkansas , Fayetteville, AR, USA.

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of variants in hunter-harvested white-tailed deer (WTD; , N = 1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly reflect an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of 'reduced susceptibility' genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.
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http://dx.doi.org/10.1080/19336896.2020.1832947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575228PMC
December 2020

Defining relictual biodiversity: Conservation units in speckled dace (Leuciscidae: ) of the Greater Death Valley ecosystem.

Ecol Evol 2020 Oct 1;10(19):10798-10817. Epub 2020 Sep 1.

Department of Biological Sciences University of Arkansas Fayetteville AR USA.

The tips in the tree of life serve as foci for conservation and management, yet clear delimitations are masked by inherent variance at the species-population interface. Analyses using thousands of nuclear loci can potentially sort inconsistencies, yet standard categories applied to this parsing are themselves potentially conflicting and/or subjective [e.g., DPS (distinct population segments); DUs (Diagnosable Units-Canada); MUs (management units); SSP (subspecies); ESUs (Evolutionarily Significant Units); and UIEUs (uniquely identified evolutionary units)]. One potential solution for consistent categorization is to create a comparative framework by accumulating statistical results from independent studies and evaluating congruence among data sets. Our study illustrates this approach in speckled dace (Leuciscidae: ) endemic to two basins (Owens and Amargosa) in the Death Valley ecosystem. These fish persist in the Mojave Desert as isolated Plio-Pleistocene relicts and are of conservation concern, but lack formal taxonomic descriptions/designations. Double digest RAD (ddRAD) methods identified 14,355 SNP loci across 10 populations ( = 140). Species delimitation analyses [multispecies coalescent (MSC) and unsupervised machine learning (UML)] delineated four putative ESUs. outlier loci ( = 106) were juxtaposed to uncover the potential for localized adaptations. We detected one hybrid population that resulted from upstream reconnection of habitat following contemporary pluvial periods, whereas remaining populations represent relics of ancient tectonism within geographically isolated springs and groundwater-fed streams. Our study offers three salient conclusions: a blueprint for a multifaceted delimitation of conservation units; a proposed mechanism by which criteria for intraspecific biodiversity can be potentially standardized; and a strong argument for the proactive management of critically endangered Death Valley ecosystem fishes.
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http://dx.doi.org/10.1002/ece3.6736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548178PMC
October 2020

Contrasting signatures of introgression in North American box turtle (Terrapene spp.) contact zones.

Mol Ecol 2020 11 11;29(21):4186-4202. Epub 2020 Sep 11.

Department of Biological Sciences, University of Arkansas, Fayetteville, AR, USA.

Hybridization occurs differentially across the genome in a balancing act between selection and migration. With the unprecedented resolution of contemporary sequencing technologies, selection and migration can now be effectively quantified such that researchers can identify genetic elements involved in introgression. Furthermore, genomic patterns can now be associated with ecologically relevant phenotypes, given availability of annotated reference genomes. We do so in North American box turtles (Terrapene) by deciphering how selection affects hybrid zones at the interface of species boundaries and identifying genetic regions potentially under selection that may relate to thermal adaptations. Such genes may impact physiological pathways involved in temperature-dependent sex determination, immune system functioning and hypoxia tolerance. We contrasted these patterns across inter- and intraspecific hybrid zones that differ temporally and biogeographically. We demonstrate hybridization is broadly apparent in Terrapene, but with observed genomic cline patterns corresponding to species boundaries at loci potentially associated with thermal adaptation. These loci display signatures of directional introgression within intraspecific boundaries, despite a genome-wide selective trend against intergrades. In contrast, outlier loci for interspecific comparisons exhibited evidence of being under selection against hybrids. Importantly, adaptations coinciding with species boundaries in Terrapene overlap with climatic boundaries and highlight the vulnerability of these terrestrial ectotherms to anthropogenic pressures.
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http://dx.doi.org/10.1111/mec.15622DOI Listing
November 2020

New insights into the food web of an Australian tropical river to inform water resource management.

Sci Rep 2020 08 31;10(1):14294. Epub 2020 Aug 31.

School of Biological Sciences, The University of Western Australia, Perth, 6009, Australia.

Rivers around the world are threatened by altered flow due to water resource development. Altered flow can change food webs and impact riverine energetics. The Fitzroy River, in northern Australia, is targeted for development but uncertainty remains about the sources of carbon supporting the food web, particularly in the lowlands-the region most likely to be impacted by water extraction. This study used stable isotopes to investigate if algal biofilm is the main carbon source sustaining fish in lowland habitats. We also sought evidence that large-bodied migratory fish were transporting remote carbon around the system. Our results revealed that local algal biofilm carbon was the dominant source of energy sustaining fish in wet season floodplain habitats, but that fish in main-channel pools during the dry season were increasingly dependent on other carbon sources, such as leaf litter or phytoplankton. We found no evidence that large-bodied fish were transporting remote carbon from the floodplain or estuary into the lower main-channel of the river. We recommend that water planners take a precautionary approach to policy until sufficient food web evidence is amassed.
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http://dx.doi.org/10.1038/s41598-020-71331-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459293PMC
August 2020

Opicinumab: is it a potential treatment for multiple sclerosis?

Ann Transl Med 2020 Jul;8(14):892

Neuroscience & Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.

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http://dx.doi.org/10.21037/atm.2020.03.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396746PMC
July 2020

ADMIXPIPE: population analyses in ADMIXTURE for non-model organisms.

BMC Bioinformatics 2020 Jul 29;21(1):337. Epub 2020 Jul 29.

Department of Biological Sciences, University of Arkansas, Fayetteville, AR, 72701, USA.

Background: Research on the molecular ecology of non-model organisms, while previously constrained, has now been greatly facilitated by the advent of reduced-representation sequencing protocols. However, tools that allow these large datasets to be efficiently parsed are often lacking, or if indeed available, then limited by the necessity of a comparable reference genome as an adjunct. This, of course, can be difficult when working with non-model organisms. Fortunately, pipelines are currently available that avoid this prerequisite, thus allowing data to be a priori parsed. An oft-used molecular ecology program (i.e., STRUCTURE), for example, is facilitated by such pipelines, yet they are surprisingly absent for a second program that is similarly popular and computationally more efficient (i.e., ADMIXTURE). The two programs differ in that ADMIXTURE employs a maximum-likelihood framework whereas STRUCTURE uses a Bayesian approach, yet both produce similar results. Given these issues, there is an overriding (and recognized) need among researchers in molecular ecology for bioinformatic software that will not only condense output from replicated ADMIXTURE runs, but also infer from these data the optimal number of population clusters (K).

Results: Here we provide such a program (i.e., ADMIXPIPE) that (a) filters SNPs to allow the delineation of population structure in ADMIXTURE, then (b) parses the output for summarization and graphical representation via CLUMPAK. Our benchmarks effectively demonstrate how efficient the pipeline is for processing large, non-model datasets generated via double digest restriction-site associated DNA sequencing (ddRAD). Outputs not only parallel those from STRUCTURE, but also visualize the variation among individual ADMIXTURE runs, so as to facilitate selection of the most appropriate K-value.

Conclusions: ADMIXPIPE successfully integrates ADMIXTURE analysis with popular variant call format (VCF) filtering software to yield file types readily analyzed by CLUMPAK. Large population genomic datasets derived from non-model organisms are efficiently analyzed via the parallel-processing capabilities of ADMIXTURE. ADMIXPIPE is distributed under the GNU Public License and freely available for Mac OSX and Linux platforms at: https://github.com/stevemussmann/admixturePipeline .
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http://dx.doi.org/10.1186/s12859-020-03701-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391514PMC
July 2020

Gene flow and species delimitation in fishes of Western North America: Flannelmouth () and Bluehead sucker ().

Ecol Evol 2020 Jul 17;10(13):6477-6493. Epub 2020 Jun 17.

Department of Biological Sciences University of Arkansas Fayetteville AR USA.

The delimitation of species boundaries, particularly those obscured by reticulation, is a critical step in contemporary biodiversity assessment. It is especially relevant for conservation and management of indigenous fishes in western North America, represented herein by two species with dissimilar life histories codistributed in the highly modified Colorado River (i.e., flannelmouth sucker, ; bluehead sucker, ). To quantify phylogenomic patterns and examine proposed taxonomic revisions, we first employed double-digest restriction site-associated DNA sequencing (ddRAD), yielding 39,755 unlinked SNPs across 139 samples. These were subsequently evaluated with multiple analytical approaches and by contrasting life history data. Three phylogenetic methods and a Bayesian assignment test highlighted similar phylogenomic patterns in each, but with considerable difference in presumed times of divergence. Three lineages were detected in bluehead sucker, supporting elevation of to species status and recognizing (Zuni bluehead sucker) as a discrete entity. Admixture in the latter necessitated a reevaluation of its contemporary and historic distributions, underscoring how biodiversity identification can be confounded by complex evolutionary histories. In addition, we defined three separate flannelmouth sucker lineages as ESUs (evolutionarily significant units), given limited phenotypic and genetic differentiation, contemporary isolation, and lack of concordance (per the genealogical concordance component of the phylogenetic species concept). Introgression was diagnosed in both species, with the Little Colorado and Virgin rivers in particular. Our diagnostic methods, and the agreement of our SNPs with previous morphological, enzymatic, and mitochondrial work, allowed us to partition complex evolutionary histories into requisite components, such as isolation versus secondary contact.
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http://dx.doi.org/10.1002/ece3.6384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381754PMC
July 2020

Reticulate evolution as a management challenge: Patterns of admixture with phylogenetic distance in endemic fishes of western North America.

Evol Appl 2020 Jul 29;13(6):1400-1419. Epub 2020 Jun 29.

Department of Biological Sciences University of Arkansas Fayetteville AR USA.

Admixture in natural populations is a long-standing management challenge, with population genomic approaches offering means for adjudication. We now more clearly understand the permeability of species boundaries and the potential of admixture for promoting adaptive evolution. These issues particularly resonate in western North America, where tectonism and aridity have fragmented and reshuffled rivers over millennia, in turn promoting reticulation among endemic fishes, a situation compounded by anthropogenic habitat modifications and non-native introductions. The melding of historic and contemporary admixture has both confused and stymied management. We underscore this situation with a case study that quantifies basin-wide admixture among a group of native and introduced fishes by employing double-digest restriction site-associated DNA (ddRAD) sequencing. Our approach: (a) quantifies the admixed history of 343 suckers (10 species of Catostomidae) across the Colorado River Basin; (b) gauges admixture within the context of phylogenetic distance and "ecological specialization"; and (c) extrapolates potential drivers of introgression across hybrid crosses that involve endemic as well as invasive species. Our study extends across an entire freshwater basin and expands previous studies more limited in scope both geographically and taxonomically. Our results detected admixture involving all 10 species, with habitat alterations not only accelerating the breakdown of reproductive isolation, but also promoting introgression. Hybridization occurred across the genus despite phylogenetic distance, whereas introgression was only detected within subgenera, implicating phylogenetic distance and/or ecological specialization as drivers of reproductive isolation. Understanding the extent of admixture and reproductive isolation across multiple species serves to disentangle their reticulate evolutionary histories and provides a broadscale perspective for basin-wide conservation and management.
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http://dx.doi.org/10.1111/eva.13042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359839PMC
July 2020

Elevated Magnesium Concentrations Altered Freshwater Assemblage Structures in a Mesocosm Experiment.

Environ Toxicol Chem 2020 10 1;39(10):1973-1987. Epub 2020 Sep 1.

Environmental Research Institute of the Supervising Scientist, Australian Government Department of the Environment and Energy, Darwin, Northern Territory, Australia.

Magnesium (Mg) is a mining-related contaminant in the Alligators Rivers Region of tropical northern Australia. A mesocosm experiment was used to assess Mg toxicity to aquatic freshwater assemblages. Twenty-five 2700-L tubs were arranged, stratified randomly, on the bed of Magela Creek, a seasonally flowing, sandy stream channel in the Alligator Rivers Region of northern Australia. The experiment comprised 5 replicates of 4 nominal Mg treatments, 2.5, 7.5, 23, and 68 mg L , and a control. Phytoplankton biomass, and diatom, zooplankton, and macroinvertebrate assemblages present in the treatment tubs were sampled before and after Mg addition. A significant negative relationship between phytoplankton biomass and Mg was observed 4 wk after Mg addition as measured by chlorophyll a concentrations (r  = 0.97, p = 0.01). This result was supported by reductions in some major phytoplankton groups in response to increasing Mg concentrations, in the same experiment and from independent field studies. There was a significant negative relationship between zooplankton assemblage similarity (to control) and Mg concentrations (r  = 0.96, p = 0.002). Seven weeks after Mg addition, macroinvertebrate assemblages were dominated by 3 microcrustacean groups (Ostracoda, Cladocera, and Copepoda), each reaching maximum abundance at intermediate Mg concentrations (i.e., unimodal responses). The responses of phytoplankton and zooplankton were used to derive assemblage effect concentrations (Mg concentrations resulting in x% of the assemblage change [ECx]). Magnesium concentrations resulting in assemblage EC01 values were <3 mg L . Together with candidate guideline values from other laboratory- and field-based lines of evidence, the mesocosm EC01 values were incorporated into a weight-of-evidence framework for a robust regulatory approach to environmental protection. Environ Toxicol Chem 2020;39:1973-1987. © 2020 Commonwealth of Australia. Published by Wiley Periodicals LLC on behalf of SETAC.
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http://dx.doi.org/10.1002/etc.4817DOI Listing
October 2020

Private Payer and Medicare Coverage for Circulating Tumor DNA Testing: A Historical Analysis of Coverage Policies From 2015 to 2019.

J Natl Compr Canc Netw 2020 07;18(7):866-872

1Department of Clinical Pharmacy, UCSF Center for Translational and Policy Research on Personalized Medicine (TRANSPERS), San Francisco.

Background: Clinical adoption of the sequencing of circulating tumor DNA (ctDNA) for cancer has rapidly increased in recent years. This sequencing is used to select targeted therapy and monitor nonresponding or progressive tumors to identify mechanisms of therapeutic resistance. Our study objective was to review available coverage policies for cancer ctDNA-based testing panels to examine trends from 2015 to 2019.

Methods: We analyzed publicly available private payer policies and Medicare national coverage determinations and local coverage determinations (LCDs) for ctDNA-based panel tests for cancer. We coded variables for each year representing policy existence, covered clinical scenario, and specific ctDNA test covered. Descriptive analyses were performed.

Results: We found that 38% of private payer coverage policies provided coverage of ctDNA-based panel testing as of July 2019. Most private payer policy coverage was highly specific: 87% for non-small cell lung cancer, 47% for EGFR gene testing, and 79% for specific brand-name tests. There were 8 final, 2 draft, and 2 future effective final LCDs (February 3 and March 15, 2020) that covered non-FDA-approved ctDNA-based tests. The draft and future effective LCDs were the first policies to cover pan-cancer use.

Conclusions: Coverage of ctDNA-based panel testing for cancer indications increased from 2015 to 2019. The trend in private payer and Medicare coverage is an increasing number of coverage policies, number of positive policies, and scope of coverage. We found that Medicare coverage policies are evolving to pan-cancer uses, signifying a significant shift in coverage frameworks. Given that genomic medicine is rapidly changing, payers and policymakers (eg, guideline developers) will need to continue to evolve policies to keep pace with emerging science and standards in clinical care.
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http://dx.doi.org/10.6004/jnccn.2020.7542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347155PMC
July 2020

Insights From a Temporal Assessment of Increases in US Private Payer Coverage of Tumor Sequencing From 2015 to 2019.

Value Health 2020 05 19;23(5):551-558. Epub 2020 Mar 19.

Center for Translational and Policy Research on Personalized Medicine, University of California at San Francisco, San Francisco, CA, USA; Philip R. Lee Institute for Health Policy, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.

Objectives: To examine the temporal trajectory of insurance coverage for next-generation tumor sequencing (sequencing) by private US payers, describe the characteristics of coverage adopters and nonadopters, and explore adoption trends relative to the Centers for Medicare and Medicaid Services' National Coverage Determination (CMS NCD) for sequencing.

Methods: We identified payers with positive coverage (adopters) or negative coverage (nonadopters) of sequencing on or before April 1, 2019, and abstracted their characteristics including size, membership in the BlueCross BlueShield Association, and whether they used a third-party policy. Using descriptive statistics, payer characteristics were compared between adopters and nonadopters and between pre-NCD and post-NCD adopters. An adoption timeline was constructed.

Results: Sixty-nine payers had a sequencing policy. Positive coverage started November 30, 2015, with 1 payer and increased to 33 (48%) as of April 1, 2019. Adopters were less likely to be BlueCross BlueShield members (P < .05) and more likely to use a third-party policy (P < .001). Fifty-eight percent of adopters were small payers. Among adopters, 52% initiated coverage pre-NCD over a 25-month period and 48% post-NCD over 17 months.

Conclusions: We found an increase, but continued variability, in coverage over 3.5 years. Temporal analyses revealed important trends: the possible contribution of the CMS NCD to a faster pace of coverage adoption, the interdependence in coverage timing among BlueCross BlueShield members, the impact of using a third-party policy on coverage timing, and the importance of small payers in early adoption. Our study is a step toward systematic temporal research of coverage for precision medicine, which will inform policy and affordability assessments.
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http://dx.doi.org/10.1016/j.jval.2020.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217867PMC
May 2020

Use of Real-World Evidence in US Payer Coverage Decision-Making for Next-Generation Sequencing-Based Tests: Challenges, Opportunities, and Potential Solutions.

Value Health 2020 05 26;23(5):540-550. Epub 2020 Mar 26.

Center for Translational and Policy Research on Personalized Medicine, Department of Clinical Pharmacy, University of California at San Francisco, San Francisco, CA, USA; Philip R. Lee Institute for Health Policy, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer, University of California at San Francisco, San Francisco, CA, USA.

Objectives: Given the potential of real-world evidence (RWE) to inform understanding of the risk-benefit profile of next-generation sequencing (NGS)-based testing, we undertook a study to describe the current landscape of whether and how payers use RWE as part of their coverage decision making and potential solutions for overcoming barriers.

Methods: We performed a scoping literature review of existing RWE evidentiary frameworks for evaluating new technologies and identified barriers to clinical integration and evidence gaps for NGS. We synthesized findings as potential solutions for improving the relevance and utility of RWE for payer decision-making.

Results: Payers require evidence of clinical utility to inform coverage decisions, yet we found a relatively small number of published RWE studies, and these are predominately focused on oncology, pharmacogenomics, and perinatal/pediatric testing. We identified 3 categories of innovation that may help address the current undersupply of RWE studies for NGS: (1) increasing use of RWE to inform outcomes-based contracting for new technologies, (2) precision medicine initiatives that integrate clinical and genomic data and enable data sharing, and (3) Food and Drug Administration reforms to encourage the use of RWE. Potential solutions include development of data and evidence review standards, payer engagement in RWE study design, use of incentives and partnerships to lower the barriers to RWE generation, education of payers and providers concerning the use of RWE and NGS, and frameworks for conducting outcomes-based contracting for NGS.

Conclusions: We provide numerous suggestions to overcome the data, methodologic, infrastructure, and policy challenges constraining greater integration of RWE in assessments of NGS.
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http://dx.doi.org/10.1016/j.jval.2020.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219085PMC
May 2020

Multi-targeted management of upland game birds at the agroecosystem interface in midwestern North America.

PLoS One 2020 27;15(4):e0230735. Epub 2020 Apr 27.

Biological Sciences, University of Arkansas, Fayetteville, Arkansas, United States of America.

Despite its imperative, biodiversity conservation is chronically underfunded, a deficiency that often forces management agencies to prioritize. Single-species recovery thus becomes a focus (often with socio-political implications), whereas a more economical approach would be the transition to multi-targeted management (= MTM). This challenge is best represented in Midwestern North America where biodiversity has been impacted by 300+ years of chronic anthropogenic disturbance such that native tall-grass prairie is now supplanted by an agroecosystem. Here, we develop an MTM with a population genetic metric to collaboratively manage three Illinois upland gamebirds: common pheasant (Phasianus colchicus; pheasant), northern bobwhite quail (Colinus virginianus; quail), and threatened-endangered (T&E) greater prairie chicken (Tympanuchus cupido pinnatus; prairie chicken). We first genotyped our study pheasant at 19 microsatellite DNA loci and identified three captive breeding stocks (N = 143; IL Department of Natural Resources) as being significantly bottlenecked, with relatedness >1st-cousin (μR = 0.158). 'Wild' (non-stocked) pheasant [N = 543; 14 Pheasant-Habitat-Areas (PHAs)] were also bottlenecked, significantly interrelated (μR = 0.150) and differentiated (μFST = 0.047), yet distinct from propagation stock. PHAs that encompassed significantly with larger areas also reflected greater effective population sizes (μNE = 43; P<0.007). We juxtaposed these data against previously published results for prairie chicken and quail, and found population genetic structure driven by drift, habitat/climate impacts, and gender-biased selection via hunter-harvest. Each species (hunter-harvested or T&E) is independently managed, yet their composite population genetic baseline provides the quantitative criteria needed for an upland game bird MTM. Its implementation would require agricultural plots to be rehabilitated/reclaimed using a land-sharing/sparing portfolio that differs markedly from the Conservation Reserve Program (CRP), where sequestered land decreases as agricultural prices escalate. Cost-savings for an MTM would accrue by synchronizing single-species management with a dwindling hunter-harvest program, and by eliminating propagation/stocking programs. This would sustain not only native grasslands and their resident species, but also accelerate conservation at the wildlife-agroecosystem interface.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230735PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185590PMC
July 2020

Understanding rivers and their social relations: A critical step to advance environmental water management.

WIREs Water 2019 ;6(6)

Australian Rivers Institute, Griffith University, Nathan, Queensland, Australia.

River flows connect people, places, and other forms of life, inspiring and sustaining diverse cultural beliefs, values, and ways of life. The concept of environmental flows provides a framework for improving understanding of relationships between river flows and people, and for supporting those that are mutually beneficial. Nevertheless, most approaches to determining environmental flows remain grounded in the biophysical sciences. The newly revised Brisbane Declaration and Global Action Agenda on Environmental Flows (2018) represents a new phase in environmental flow science and an opportunity to better consider the co-constitution of river flows, ecosystems, and society, and to more explicitly incorporate these relationships into river management. We synthesize understanding of relationships between people and rivers as conceived under the renewed definition of environmental flows. We present case studies from Honduras, India, Canada, New Zealand, and Australia that illustrate multidisciplinary, collaborative efforts where recognizing and meeting diverse flow needs of human populations was central to establishing environmental flow recommendations. We also review a small body of literature to highlight examples of the diversity and interdependencies of human-flow relationships-such as the linkages between river flow and human well-being, spiritual needs, cultural identity, and sense of place-that are typically overlooked when environmental flows are assessed and negotiated. Finally, we call for scientists and water managers to recognize the diversity of ways of knowing, relating to, and utilizing rivers, and to place this recognition at the center of future environmental flow assessments. This article is categorized under: Water and Life > Conservation, Management, and Awareness Human Water > Water Governance Human Water > Water as Imagined and Represented.
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http://dx.doi.org/10.1002/wat2.1381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905518PMC
January 2019

Tracking the resource pulse: Movement responses of fish to dynamic floodplain habitat in a tropical river.

J Anim Ecol 2020 03 26;89(3):795-807. Epub 2019 Dec 26.

NESP Northern Australia Environmental Resources Hub, School of Biological Sciences, The University of Western Australia, Crawley, WA, Australia.

Natural river floodplains are among the Earth's most biologically diverse and productive ecosystems but face a range of critical threats due to human disturbance. Understanding the ecological processes that support biodiversity and productivity in floodplain rivers is essential for their future protection and rehabilitation. Fish assemblage structure on tropical river floodplains is widely considered to be driven by dispersal limitation during the wet season and by environmental filtering and interspecific interactions during the dry season. However, the individual-level movement behaviours (e.g. site attachment, nomadism, homing) that regulate dispersal of fish on floodplains are poorly understood. We combined radiotelemetry and remote sensing to examine the movement behaviour of two large-bodied fishes (barramundi Lates calcarifer, forktail catfish Neoarius leptaspis) over the flood cycle in a tropical river-floodplain system in northern Australia to: (a) quantify movement responses in relation to dynamic habitat resources at a landscape scale; and (b) determine the extent of spatial 'reshuffling' of individual fish following the wet season. Both species altered their behaviour rapidly in response to changes in the availability and distribution of aquatic habitat, with most individuals undertaking extensive movements (up to ~27 km from the tagging location) on the inundated floodplain during the wet season. Although there was considerable individual variation in movement patterns, overall barramundi distributions closely tracked the extent of floodplain primary productivity, whereas catfish distributions were most closely associated with the extent of flooded area. Most individuals of both species exhibited homing back to previously occupied dry season refugia during the wet-to-dry transition, even though other potential refugia were available in closer proximity to wet season activity areas. We postulate that homing behaviour modulates temporal variation in fish assemblage composition and abundance and limits the transfer of aquatic-derived energy and nutrients into terrestrial food webs by reducing fish mortality on drying floodplains. Our study demonstrates the importance of quantifying individual-level behaviour across the three stages of dispersal (emigration, inter-patch movement, immigration) for our understanding of how animal movement influences energetic subsidies and other large-scale ecosystem processes.
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http://dx.doi.org/10.1111/1365-2656.13146DOI Listing
March 2020

Balloon-assisted remote external iliac artery endarterectomy: A safe and durable technique for the treatment of iliac artery occlusive disease.

J Vasc Surg 2020 06 11;71(6):2029-2037. Epub 2019 Nov 11.

Mission Hospitals, Asheville, NC.

Background: Historically, the treatment of iliac artery occlusive disease required a surgical bypass usually consisting of an aortobifemoral bypass or an iliofemoral bypass. With the advent of balloon angioplasty and stenting, these procedures are frequently replaced with endovascular options. However, the treatment of diffuse occlusive disease of the external iliac artery (EIA) using balloon angioplasty and/or stenting does not carry a favorable long-term patency rate. Remote endarterectomy of the EIA using ring dissectors with balloon assistance provides a novel, controlled, safe, and durable treatment of the diseased and/or occluded EIA.

Methods: A retrospective review over the past 6 years was performed at our institution identifying patients treated with balloon-assisted remote endarterectomy of the EIA by the current five practicing vascular surgeons. The technique involves exposure of the ipsilateral common femoral artery. With nonocclusive disease, direct access into the common femoral artery is performed, a wire is traversed through the diseased EIA, and a balloon is inflated at the origin of the vessel providing hemostasis and control. A femoral endarterectomy is performed, and a ring dissector is passed over the endarterectomized material including the wire and balloon catheter and advanced remotely through the EIA up to the balloon. The balloon is briefly deflated, repositioned within the ring dissector, and reinflated, thus cutting the plaque. This allows for retraction of the inflated balloon and cutter, removing the endarterectomized core plaque. The procedure is similar for the treatment of an occluded EIA, but wire access across the occluded vessel is normally achieved with contralateral access. In both cases, the balloon provides control and hemostasis and is critically important in the rare treatment of vessel rupture.

Results: A total of 101 vessels were treated in 97 patients. The procedure was successful in 98 vessels (97%) with failure related to vessel rupture requiring conversion to an iliofemoral bypass. The estimated patency rate at three years was 94% with a median follow-up of 20 months. Restenosis/occlusion in four patients seemed to be related to a severe sclerotic response. The EIA was occluded 32% of the time. The common iliac artery (CIA) was diseased requiring angioplasty and stenting 29% of the time and a stent was placed at the transition zone between endarterectomized vessel and nontreated proximal most EIA or distal most CIA 58% of the time. There were no perioperative deaths.

Conclusions: Balloon-assisted remote endarterectomy of the diffusely diseased and/or occluded EIA is a safe and durable option. It precludes the need for a prosthetic conduit and the risk of associated infection. It also involves a single groin incision and negates the need for retroperitoneal exposure of the CIA.
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http://dx.doi.org/10.1016/j.jvs.2019.08.263DOI Listing
June 2020
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