Publications by authors named "Mark G Thomas"

155 Publications

The impact of the Auckland cellulitis pathway on length of hospital stay, mortality readmission rate, and antibiotic stewardship.

Clin Infect Dis 2021 Feb 26. Epub 2021 Feb 26.

Department of Infectious Diseases, Auckland District Health Board, Auckland, New Zealand.

Background: The Dundee classification of cellulitis severity, previously shown to predict disease outcomes, provides an opportunity to improve the management of patients with cellulitis.

Methods: We developed and implemented a pathway to guide the management of adults with cellulitis based on their Dundee severity class, and measured its effect on patient outcomes. We compared the outcomes in patients admitted to Auckland City Hospital (ACH) between July 2014 and July 2015 (the baseline cohort) with those in patients admitted between June 2017 and June 2018 (the intervention cohort).

Results: The median length of stay was shorter in the intervention cohort (0.7 days, IQR 0.1 to 3.0 days) than in the baseline cohort (1.8 days, IQR 0.1 to 4.4 days; P<0.001). The 30 day mortality rate declined from 1.8% (19/1092) in the baseline cohort to 0.7% (10/1362; P=0.02) in the intervention cohort. The 30 day cellulitis readmission rate increased from 6% in the baseline cohort to 11% (P<0.001) in the intervention cohort. Adherence to the ACH cellulitis antibiotic guideline improved from 38% to 48% (P<0.01) and was independently associated with reduced length of stay.

Conclusions: The implementation of the Auckland cellulitis pathway, readily generalizable to other settings, improved the outcomes in patients with cellulitis, and resulted in an annual saving of approximately 1,000 bed days.
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http://dx.doi.org/10.1093/cid/ciab181DOI Listing
February 2021

Directly modelling population dynamics in the South American Arid Diagonal using C dates.

Philos Trans R Soc Lond B Biol Sci 2021 Jan 30;376(1816):20190723. Epub 2020 Nov 30.

Department of Geography, King's College London, Strand, London WC2R 2LS, UK.

Large anthropogenic C datasets are widely used to generate summed probability distributions (SPDs) as a proxy for past human population levels. However, SPDs are a poor proxy when datasets are small, bearing little relationship to true population dynamics. Instead, more robust inferences can be achieved by directly modelling the population and assessing the model likelihood given the data. We introduce the R package ADMUR which uses a continuous piecewise linear (CPL) model of population change, calculates the model likelihood given a C dataset, estimates credible intervals using Markov chain Monte Carlo, applies a goodness-of-fit test, and uses the Schwarz Criterion to compare CPL models. We demonstrate the efficacy of this method using toy data, showing that spurious dynamics are avoided when sample sizes are small, and true population dynamics are recovered as sample sizes increase. Finally, we use an improved C dataset for the South American Arid Diagonal to compare CPL modelling to current simulation methods, and identify three Holocene phases when population trajectory estimates changed from rapid initial growth of 4.15% per generation to a decline of 0.05% per generation between 10 821 and 7055 yr BP, then gently grew at 0.58% per generation until 2500 yr BP. This article is part of the theme issue 'Cross-disciplinary approaches to prehistoric demography'.
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http://dx.doi.org/10.1098/rstb.2019.0723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7741102PMC
January 2021

Low Prevalence of Lactase Persistence in Bronze Age Europe Indicates Ongoing Strong Selection over the Last 3,000 Years.

Curr Biol 2020 Nov 3;30(21):4307-4315.e13. Epub 2020 Sep 3.

Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland; Swiss Institute of Bioinformatics, 1700 Fribourg, Switzerland. Electronic address:

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years.
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http://dx.doi.org/10.1016/j.cub.2020.08.033DOI Listing
November 2020

XAF1 as a modifier of p53 function and cancer susceptibility.

Sci Adv 2020 Jun 24;6(26):eaba3231. Epub 2020 Jun 24.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Cancer risk is highly variable in carriers of the common R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma ( = 0.003) and subsequent malignancies ( = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic variants, whereas -E134* is markedly attenuated in this activity. We propose that cosegregation of E134* and R337H mutations leads to a more aggressive cancer phenotype than R337H alone, with implications for genetic counseling and clinical management of hypomorphic mutant carriers.
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http://dx.doi.org/10.1126/sciadv.aba3231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314530PMC
June 2020

Ancient West African foragers in the context of African population history.

Nature 2020 01 22;577(7792):665-670. Epub 2020 Jan 22.

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group. One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region. However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.
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http://dx.doi.org/10.1038/s41586-020-1929-1DOI Listing
January 2020

A 3,000-year-old Egyptian emmer wheat genome reveals dispersal and domestication history.

Nat Plants 2019 11 4;5(11):1120-1128. Epub 2019 Nov 4.

Genetics Institute, Research Department of Genetics, Evolution and Environment, University College London, London, UK.

Tetraploid emmer wheat (Triticum turgidum ssp. dicoccon) is a progenitor of the world's most widely grown crop, hexaploid bread wheat (Triticum aestivum), as well as the direct ancestor of tetraploid durum wheat (T. turgidum subsp. turgidum). Emmer was one of the first cereals to be domesticated in the old world; it was cultivated from around 9700 BC in the Levant and subsequently in south-western Asia, northern Africa and Europe with the spread of Neolithic agriculture. Here, we report a whole-genome sequence from a museum specimen of Egyptian emmer wheat chaff, C dated to the New Kingdom, 1130-1000 BC. Its genome shares haplotypes with modern domesticated emmer at loci that are associated with shattering, seed size and germination, as well as within other putative domestication loci, suggesting that these traits share a common origin before the introduction of emmer to Egypt. Its genome is otherwise unusual, carrying haplotypes that are absent from modern emmer. Genetic similarity with modern Arabian and Indian emmer landraces connects ancient Egyptian emmer with early south-eastern dispersals, whereas inferred gene flow with wild emmer from the Southern Levant signals a later connection. Our results show the importance of museum collections as sources of genetic data to uncover the history and diversity of ancient cereals.
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http://dx.doi.org/10.1038/s41477-019-0534-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858886PMC
November 2019

Beyond multiregional and simple out-of-Africa models of human evolution.

Nat Ecol Evol 2019 10;3(10):1370-1372

Research Department of Genetics, Evolution and Environment, University College London, London, UK.

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http://dx.doi.org/10.1038/s41559-019-0992-1DOI Listing
October 2019

Long-Term Stable Bone Mineral Density in HIV-Infected Men Without Risk Factors for Osteoporosis Treated with Antiretroviral Therapy.

Calcif Tissue Int 2019 10 27;105(4):423-429. Epub 2019 Jun 27.

Department of Medicine, University of Auckland, Auckland, New Zealand.

Introduction: Most prospective studies of bone mineral density (BMD) in HIV-infected cohorts taking antiretroviral therapy (ART) have been of short duration, typically < 3 years. Such studies have reported short-term stable or increasing BMD. We assessed whether this BMD stability persists for > 10 years in middle-aged and older men established on ART.

Methods: A 12-year, prospective, longitudinal study in 44 HIV-infected men treated with ART who had measurements of BMD at the lumbar spine, proximal femur and total body at baseline, 2, 6 and 12 years.

Results: At baseline, the mean age of participants was 49 years, the mean duration of HIV infection was 8 years, and the mean duration of ART was 50 months. After 12 years, BMD increased by 6.9% (95% CI 3.4 to 10.3) at the lumbar spine, and remained stable (range of BMD change: - 0.6% to 0.0%) at the total hip, femoral neck and total body. Only two individuals had a decrease of > 10% in BMD at any site during follow-up and both decreases in BMD were explained by co-morbid illnesses.

Conclusions: BMD remained stable over 12 years in middle-aged and older HIV-infected men treated with ART. Monitoring BMD in men established on ART who do not have risk factors for BMD loss is not necessary.
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http://dx.doi.org/10.1007/s00223-019-00579-0DOI Listing
October 2019

Transmission of HIV infection by severe bites.

Int J STD AIDS 2019 08 21;30(9):927-929. Epub 2019 Jun 21.

2 Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand.

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http://dx.doi.org/10.1177/0956462419844852DOI Listing
August 2019

A Rare Deep-Rooting D0 African Y-Chromosomal Haplogroup and Its Implications for the Expansion of Modern Humans Out of Africa.

Genetics 2019 08 13;212(4):1421-1428. Epub 2019 Jun 13.

The Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK

Present-day humans outside Africa descend mainly from a single expansion out ∼50,000-70,000 years ago, but many details of this expansion remain unclear, including the history of the male-specific Y chromosome at this time. Here, we reinvestigate a rare deep-rooting African Y-chromosomal lineage by sequencing the whole genomes of three Nigerian men described in 2003 as carrying haplogroup DE* Y chromosomes, and analyzing them in the context of a calibrated worldwide Y-chromosomal phylogeny. We confirm that these three chromosomes do represent a deep-rooting DE lineage, branching close to the DE bifurcation, but place them on the D branch as an outgroup to all other known D chromosomes, and designate the new lineage D0. We consider three models for the expansion of Y lineages out of Africa ∼50,000-100,000 years ago, incorporating migration back to Africa where necessary to explain present-day Y-lineage distributions. Considering both the Y-chromosomal phylogenetic structure incorporating the D0 lineage, and published evidence for modern humans outside Africa, the most favored model involves an origin of the DE lineage within Africa with D0 and E remaining there, and migration out of the three lineages (C, D, and FT) that now form the vast majority of non-African Y chromosomes. The exit took place 50,300-81,000 years ago (latest date for FT lineage expansion outside Africa - earliest date for the D/D0 lineage split inside Africa), and most likely 50,300-59,400 years ago (considering Neanderthal admixture). This work resolves a long-running debate about Y-chromosomal out-of-Africa/back-to-Africa migrations, and provides insights into the out-of-Africa expansion more generally.
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http://dx.doi.org/10.1534/genetics.119.302368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707464PMC
August 2019

Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism.

Elife 2019 06 4;8. Epub 2019 Jun 4.

Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining , strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22's role in metabolism and have potential to differentially influence the human insulin response.
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http://dx.doi.org/10.7554/eLife.41517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548504PMC
June 2019

The use of a poster to reduce expectations to receive antibiotics for a common cold.

Eur J Clin Microbiol Infect Dis 2019 Aug 17;38(8):1463-1469. Epub 2019 May 17.

Faculty of Business and Economics, University of Auckland, Auckland, New Zealand.

Many doctors prescribe antibiotics for a cold, to meet patient's expectations. As a result, patient's education about antibiotics and antibiotic resistance forms a major component of the WHO's Global Action Plan on Antimicrobial Resistance. However, it is not known whether simple educational material can change a person's attitudes about antibiotic therapy. We designed three posters about antibiotic treatment for "cold and flu". Hospital inpatients answered a baseline survey and then were asked to look at one of three randomly selected posters. The posters highlighted the futility of antibiotic treatment for colds (futility), the risk of adverse drug reactions from antibiotics (harm), and the issue of antimicrobial resistance (resistance). Participants then completed a follow-up survey. Participants' expectations to receive antibiotics for a "bad cold" reduced significantly after viewing a poster (82/299, 27% expected antibiotics in the baseline survey compared with 13% in the follow-up survey, P < 0.01). Continuing expectation to receive antibiotics after viewing one of the posters was associated with expectation to receive antibiotics in the baseline survey and the strong belief that colds were caused by bacteria. Participants who viewed the resistance poster were more likely to continue to expect antibiotics than participants who viewed the futility poster (OR 2.46, 95%CI 1.16-5.20, P = 0.02). Following discussion of the study, viewing a poster reduced participants' expectations to receive antibiotics for a hypothetical cold. Changing patients' expectations to receive antibiotics using simple educational material about antibiotic futility could lead to significant reductions in antibiotic prescription for viral upper respiratory tract infections.
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http://dx.doi.org/10.1007/s10096-019-03572-5DOI Listing
August 2019

The Arrival of Siberian Ancestry Connecting the Eastern Baltic to Uralic Speakers further East.

Curr Biol 2019 05 9;29(10):1701-1711.e16. Epub 2019 May 9.

Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. Electronic address:

In this study, we compare the genetic ancestry of individuals from two as yet genetically unstudied cultural traditions in Estonia in the context of available modern and ancient datasets: 15 from the Late Bronze Age stone-cist graves (1200-400 BC) (EstBA) and 6 from the Pre-Roman Iron Age tarand cemeteries (800/500 BC-50 AD) (EstIA). We also included 5 Pre-Roman to Roman Iron Age Ingrian (500 BC-450 AD) (IngIA) and 7 Middle Age Estonian (1200-1600 AD) (EstMA) individuals to build a dataset for studying the demographic history of the northern parts of the Eastern Baltic from the earliest layer of Mesolithic to modern times. Our findings are consistent with EstBA receiving gene flow from regions with strong Western hunter-gatherer (WHG) affinities and EstIA from populations related to modern Siberians. The latter inference is in accordance with Y chromosome (chrY) distributions in present day populations of the Eastern Baltic, as well as patterns of autosomal variation in the majority of the westernmost Uralic speakers [1-5]. This ancestry reached the coasts of the Baltic Sea no later than the mid-first millennium BC; i.e., in the same time window as the diversification of west Uralic (Finnic) languages [6]. Furthermore, phenotypic traits often associated with modern Northern Europeans, like light eyes, hair, and skin, as well as lactose tolerance, can be traced back to the Bronze Age in the Eastern Baltic. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cub.2019.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544527PMC
May 2019

Author Correction: Ancient genomes indicate population replacement in Early Neolithic Britain.

Nat Ecol Evol 2019 Jun;3(6):986-987

Department of Earth Sciences, Natural History Museum, London, UK.

In the version of this Article originally published, there were errors in the colour ordering of the legend in Fig. 5b, and in the positions of the target and surrogate populations in Fig. 5c. This has now been corrected. The conclusions of the study are in no way affected. The errors have been corrected in the HTML and PDF versions of the article.
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http://dx.doi.org/10.1038/s41559-019-0912-4DOI Listing
June 2019

Ancient genomes indicate population replacement in Early Neolithic Britain.

Nat Ecol Evol 2019 05 15;3(5):765-771. Epub 2019 Apr 15.

Department of Earth Sciences, Natural History Museum, London, UK.

The roles of migration, admixture and acculturation in the European transition to farming have been debated for over 100 years. Genome-wide ancient DNA studies indicate predominantly Aegean ancestry for continental Neolithic farmers, but also variable admixture with local Mesolithic hunter-gatherers. Neolithic cultures first appear in Britain circa 4000 BC, a millennium after they appeared in adjacent areas of continental Europe. The pattern and process of this delayed British Neolithic transition remain unclear. We assembled genome-wide data from 6 Mesolithic and 67 Neolithic individuals found in Britain, dating 8500-2500 BC. Our analyses reveal persistent genetic affinities between Mesolithic British and Western European hunter-gatherers. We find overwhelming support for agriculture being introduced to Britain by incoming continental farmers, with small, geographically structured levels of hunter-gatherer ancestry. Unlike other European Neolithic populations, we detect no resurgence of hunter-gatherer ancestry at any time during the Neolithic in Britain. Genetic affinities with Iberian Neolithic individuals indicate that British Neolithic people were mostly descended from Aegean farmers who followed the Mediterranean route of dispersal. We also infer considerable variation in pigmentation levels in Europe by circa 6000 BC.
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http://dx.doi.org/10.1038/s41559-019-0871-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520225PMC
May 2019

Food Income and the Evolution of Forager Mobility.

Sci Rep 2019 04 1;9(1):5438. Epub 2019 Apr 1.

Research Department of Genetics, Evolution & Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.

Forager mobility tends to be high, although ethnographic studies indicate ecological factors such as resource abundance and reliability, population density and effective temperature influence the cost-to-benefit assessment of movement decisions. We investigate the evolution of mobility using an agent-based and spatially explicit cultural evolutionary model that considers the feedback between foragers and their environment. We introduce Outcomes Clustering, an approach to categorizing simulated system states arising from complex stochastic processes shaped by multiple interacting parameters. We find that decreased mobility evolves under conditions of high resource replenishment and low resource depletion, with a concomitant trend of increased population density and, counter-intuitively, decreased food incomes. Conversely, increased mobility co-occurs with lower population densities and higher food incomes. We replicate the well-known relationships between mobility, population density, and resource quality, while predicting reduced food income, and consequently the reduction in health status observed in early sedentary populations without the need to invoke factors such as reduced diet quality or increased pathogen loads.
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http://dx.doi.org/10.1038/s41598-019-42006-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443647PMC
April 2019

Effects of Intravenous Zoledronate on Bone Turnover and Bone Density Persist for at Least 11 Years in HIV-Infected Men.

J Bone Miner Res 2019 07 29;34(7):1248-1253. Epub 2019 May 29.

Department of Medicine, University of Auckland, Auckland, New Zealand.

Previously we reported the results of a 4-year extension of a 2-year randomized placebo-controlled trial showing that the antiresorptive effects of two annual 4-mg doses of zoledronate in HIV-infected men persisted for at least 5 years after the second dose. We set out to determine whether the effects on BMD and bone turnover persist beyond 10 years. We invited all participants in the original trial known to be alive and living in New Zealand to attend an additional visit approximately 12 years after trial entry and 11 years after their second dose of study medication. The outcome measures were BMD at the lumbar spine, proximal femur, and total body, and markers of bone turnover. Twenty-five of the 43 men originally enrolled in the trial attended the final visit, representing 25 of 31 (81%) participants alive and residing in New Zealand at the time. The average duration of follow-up was 12.4 years. At the final visit, BMD remained higher in the zoledronate group than the placebo group (lumbar spine 3.7%, 95% CI, 0.1 to 7.3; total hip 3.7%, 95% CI, 1.2 to 6.2; femoral neck 5.0%, 95% CI, 2.1 to 7.9; total body 2.4%, 95% CI, 0.7 to 4.0), and the between-group differences in BMD remained stable between 6 and 12 years. Serum CTx remained lower in the zoledronate group than the placebo group between 6 and 12 years and, at the final visit, was 45% lower (95% CI, 25 to 64) than the placebo group. P1NP was 26% (95% CI, 4 to 48) lower in the zoledronate group than the placebo group at the final visit. In summary, two annual 4-mg doses of zoledronate have effects on bone turnover and BMD in men that persist for at least 11 years after the second dose. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3712DOI Listing
July 2019

Impact of a smartphone app on prescriber adherence to antibiotic guidelines in adult patients with community acquired pneumonia or urinary tract infections.

PLoS One 2019 29;14(1):e0211157. Epub 2019 Jan 29.

National Institute for Health Innovation, University of Auckland, Glen Innes, Auckland, New Zealand.

Background: Mobile phone apps have been shown to enhance guideline adherence by prescribers, but have not been widely evaluated for their impact on guideline adherence by prescribers caring for inpatients with infections.

Objectives: To determine whether providing the Auckland City Hospital (ACH) antibiotic guidelines in a mobile phone app increased guideline adherence by prescribers caring for inpatients with community acquired pneumonia (CAP) or urinary tract infections (UTIs).

Methods: We audited antibiotic prescribing during the first 24 hours after hospital admission in adults admitted during a baseline and an intervention period to determine whether provision of the app increased the level of guideline adherence. To control for changes in prescriber adherence arising from other factors, we performed similar audits of adherence to antibiotic guidelines in two adjacent hospitals.

Results: The app was downloaded by 145 healthcare workers and accessed a total of 3985 times during the three month intervention period. There was an increase in adherence to the ACH antibiotic guidelines by prescribers caring for patients with CAP from 19% (37/199) to 27% (64/237) in the intervention period (p = 0.04); but no change in guideline adherence at an adjacent hospital. There was no change in adherence to the antibiotic guidelines by prescribers caring for patients with UTI at ACH or at the two adjacent hospitals.

Conclusions: Provision of antibiotic guidelines in a mobile phone app can significantly increase guideline adherence by prescribers. However, providing an app which allows easy access to antibiotic guidelines is not sufficient to achieve high levels of prescriber adherence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350960PMC
October 2019

Genetic legacy of state centralization in the Kuba Kingdom of the Democratic Republic of the Congo.

Proc Natl Acad Sci U S A 2019 01 24;116(2):593-598. Epub 2018 Dec 24.

University College London Genetics Institute, University College London, London WC1E 6BT, United Kingdom;

Few phenomena have had as profound or long-lasting consequences in human history as the emergence of large-scale centralized states in the place of smaller scale and more local societies. This study examines a fundamental, and yet unexplored, consequence of state formation: its genetic legacy. We studied the genetic impact of state centralization during the formation of the eminent precolonial Kuba Kingdom of the Democratic Republic of the Congo (DRC) in the 17th century. We analyzed genome-wide data from over 690 individuals sampled from 27 different ethnic groups from the Kasai Central Province of the DRC. By comparing genetic patterns in the present-day Kuba, whose ancestors were part of the Kuba Kingdom, with those in neighboring non-Kuba groups, we show that the Kuba today are more genetically diverse and more similar to other groups in the region than expected, consistent with the historical unification of distinct subgroups during state centralization. We also found evidence of genetic mixing dating to the time of the Kingdom at its most prominent. Using this unique dataset, we characterize the genetic history of the Kasai Central Province and describe the historic late wave of migrations into the region that contributed to a Bantu-like ancestry component found across large parts of Africa today. Taken together, we show the power of genetics to evidence events of sociopolitical importance and highlight how DNA can be used to better understand the behaviors of both people and institutions in the past.
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http://dx.doi.org/10.1073/pnas.1811211115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329964PMC
January 2019

Genetic evidence for a western Chinese origin of broomcorn millet ().

Holocene 2018 Dec 14;28(12):1968-1978. Epub 2018 Sep 14.

Department of Archaeology and Anthropology, University of Cambridge, UK.

Broomcorn millet () is a key domesticated cereal that has been associated with the north China centre of agricultural origins. Early archaeobotanical evidence for this crop has generated two major debates. First, its contested presence in pre-7000 cal. BP sites in eastern Europe has admitted the possibility of a western origin. Second, its occurrence in the 7th and 8th millennia cal. BP in diverse regions of northern China is consistent with several possible origin foci, associated with different Neolithic cultures. We used microsatellite and () genotype data from 341 landrace samples across Eurasia, including 195 newly genotyped samples from China, to address these questions. A spatially explicit discriminative modelling approach favours an eastern Eurasian origin for the expansion of broomcorn millet. This is consistent with recent archaeobotanical and chronological re-evaluations, and stable isotopic data. The same approach, together with the distribution of alleles, is also suggestive that the origin of broomcorn millet expansion was in western China. This second unexpected finding stimulates new questions regarding the ecology of wild millet and vegetation dynamics in China prior to the mid-Holocene domestication of millet. The chronological relationship between population expansion and domestication is unclear, but our analyses are consistent with the western Loess Plateau being at least one region of primary domestication of broomcorn millet. Patterns of genetic variation indicate that this region was the source of populations to the west in Eurasia, which broomcorn probably reached via the Inner Asia Mountain Corridor from the 3rd millennium BC. A secondary westward expansion along the steppe may have taken place from the 2nd millennium BC.
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http://dx.doi.org/10.1177/0959683618798116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236650PMC
December 2018

Association of the Dundee severity classification with mortality, length of stay and readmission in adult inpatients with cellulitis.

J Antimicrob Chemother 2019 01;74(1):200-206

Department of Infectious Diseases, Auckland District Health Board, Auckland, New Zealand.

Background: The Dundee classification is a simple severity assessment tool that could optimize treatment decisions and clinical outcomes in adult patients with cellulitis; however, it has not been validated in a large cohort.

Objectives: To determine whether the Dundee classification reliably identified those patients with cellulitis who had a higher mortality, a longer length of hospital stay or an increased risk of readmission.

Methods: We performed a retrospective study of all adults with a primary discharge diagnosis of cellulitis admitted to Auckland City Hospital from August 2013 to June 2015. We classified patients by severity using the Dundee scoring system.

Results: The 30 day all-cause mortality in adult patients with a discharge diagnosis of cellulitis was 2% (29/1462) overall, and was 1% (10/806), 2% (6/271), 3% (10/353) and 9% (3/32) in Classes 1, 2, 3 and 4 of the Dundee classification, respectively (P = 0.01). Mortality was strongly associated with age >65 years (OR 9.37, 95% CI 3.00-41.23) and with heart failure (OR 6.16, 95% CI 2.73-14.23). There were significant associations between the Dundee classification and the incidence of bacteraemia, the length of hospital stay and the rate of readmission to hospital.

Conclusions: The Dundee classification is a simple, reliable tool that can be easily applied in clinical settings to predict risk of mortality in order to determine which patients can be managed in the community with oral or intravenous therapy, and which require inpatient care.
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http://dx.doi.org/10.1093/jac/dky400DOI Listing
January 2019

Efficacy and acceptability of treatment to eradicate nasal Staphylococcus aureus carriage among haemodialysis patients.

Nephrology (Carlton) 2019 Jul 24;24(7):744-750. Epub 2019 Apr 24.

School of Medical Sciences, University of Auckland, Dunedin, New Zealand.

Aim: For patients requiring haemodialysis, the risk of Staphylococcus aureus disease is higher in those colonized and persists while the person requires haemodialysis, necessitating frequent decolonization. However, the duration of successful decolonization is not known. This study aimed to determine the duration of efficacy of decolonization in intermittent and persistent S. aureus carriers requiring haemodialysis using two decolonization strategies.

Methods: We screened 100 outpatients requiring haemodialysis for S. aureus carriage and then decolonized 14 intermittent carriers and 18 persistent carriers. Participants were invited to undertake two decolonization attempts, using systemic or topical antibiotics 12 weeks apart. Nasal swabs were taken weekly to determine the duration of successful decolonization.

Results: Decolonization was successful in 24/32 (75%) participants and the median duration of decolonization was 35 days (95% confidence interval (CI) 11-59). The median duration of S. aureus decolonization was significantly shorter for persistent carriers (19 days, 95% CI 13-25 days) in comparison with intermittent carriers (70 days, 95% CI 61-79 days; P < 0.01). 28/52 (54%) post-decolonization surveys indicated that they would use the treatment again, 14/52 (27%) surveys indicated that they would not use the treatment again, and 10/52 (19%) were undecided. 16/53 (30%) decolonization attempts resulted in an adverse drug reaction.

Conclusion: Staphylococcus aureus decolonization using topical or systemic treatments was successful for many haemodialysis patients, and provided a month free of S. aureus colonization. Although decolonization treatment provided a shorter duration of success for persistent carriers in comparison with intermittent carriers, persistent carriers are likely to gain the most from effective decolonization strategies.
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http://dx.doi.org/10.1111/nep.13474DOI Listing
July 2019

Staphylococcus aureus colonisation and its relationship with skin and soft tissue infection in New Zealand children.

Eur J Clin Microbiol Infect Dis 2018 Oct 31;37(10):2001-2010. Epub 2018 Jul 31.

Infectious Diseases Department, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand.

New Zealand children suffer from high rates of skin and soft tissue infection (SSTI). Staphylococcus aureus colonisation is known to increase the risk of nosocomial infection. We aimed to determine whether S. aureus colonisation also increased the risk of community-onset SSTI. This study, performed within the Growing Up in New Zealand cohort, used interview and administrative data, and bacterial culture results from the nose, throat, and skin swabs collected at 4½ years of age. Multivariable log-binomial regression was used to derive adjusted risk ratios. S. aureus was isolated from 2225/5126 (43.4%) children. SSTI affected 1509/5126 (29.4%) children before age five. S. aureus colonisation at any site was associated with SSTI (aRR = 1.09, 95%CI 1.01-1.19), particularly in the year prior to swab collection (aRR = 1.18, 95%CI 1.02-1.37). The strongest association was between skin colonisation and SSTI within the year prior to swab collection (aRR = 1.47, 95%CI 1.14-1.84). Socioeconomic and ethnic variables remained independent determinants of SSTI. S. aureus colonisation was associated with an increased risk of community-onset SSTI. Socioeconomic and ethnic factors and eczema had independent effects on SSTI risk. Interventions which reduce the prevalence of S. aureus colonisation may be expected to reduce the incidence of community-onset SSTI.
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http://dx.doi.org/10.1007/s10096-018-3336-1DOI Listing
October 2018

Did Our Species Evolve in Subdivided Populations across Africa, and Why Does It Matter?

Trends Ecol Evol 2018 08 11;33(8):582-594. Epub 2018 Jul 11.

Laboratoire Évolution & Diversité Biologique (EDB UMR 5174), Université de Toulouse Midi-Pyrénées, CNRS, IRD, UPS. 118 route de Narbonne, Bat 4R1, 31062 Toulouse cedex 9, France; Instituto Gulbenkian de Ciência, P-2780-156, Oeiras, Portugal.

We challenge the view that our species, Homo sapiens, evolved within a single population and/or region of Africa. The chronology and physical diversity of Pleistocene human fossils suggest that morphologically varied populations pertaining to the H. sapiens clade lived throughout Africa. Similarly, the African archaeological record demonstrates the polycentric origin and persistence of regionally distinct Pleistocene material culture in a variety of paleoecological settings. Genetic studies also indicate that present-day population structure within Africa extends to deep times, paralleling a paleoenvironmental record of shifting and fractured habitable zones. We argue that these fields support an emerging view of a highly structured African prehistory that should be considered in human evolutionary inferences, prompting new interpretations, questions, and interdisciplinary research directions.
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http://dx.doi.org/10.1016/j.tree.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092560PMC
August 2018

Synchronous diversification of Sulawesi's iconic artiodactyls driven by recent geological events.

Proc Biol Sci 2018 04;285(1876)

The Palaeogenomics & Bio-Archaeology Research Network, Research Laboratory for Archaeology and History of Art, University of Oxford, Oxford OX1 3QY, UK

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that much of Sulawesi's fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric datasets derived from Sulawesi's three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.
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http://dx.doi.org/10.1098/rspb.2017.2566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904307PMC
April 2018

Erratum: The Beaker phenomenon and the genomic transformation of northwest Europe.

Authors:
Iñigo Olalde Selina Brace Morten E Allentoft Ian Armit Kristian Kristiansen Thomas Booth Nadin Rohland Swapan Mallick Anna Szécsényi-Nagy Alissa Mittnik Eveline Altena Mark Lipson Iosif Lazaridis Thomas K Harper Nick Patterson Nasreen Broomandkhoshbacht Yoan Diekmann Zuzana Faltyskova Daniel Fernandes Matthew Ferry Eadaoin Harney Peter de Knijff Megan Michel Jonas Oppenheimer Kristin Stewardson Alistair Barclay Kurt Werner Alt Corina Liesau Patricia Ríos Concepción Blasco Jorge Vega Miguel Roberto Menduiña García Azucena Avilés Fernández Eszter Bánffy Maria Bernabò-Brea David Billoin Clive Bonsall Laura Bonsall Tim Allen Lindsey Büster Sophie Carver Laura Castells Navarro Oliver E Craig Gordon T Cook Barry Cunliffe Anthony Denaire Kirsten Egging Dinwiddy Natasha Dodwell Michal Ernée Christopher Evans Milan Kuchařík Joan Francès Farré Chris Fowler Michiel Gazenbeek Rafael Garrido Pena María Haber-Uriarte Elżbieta Haduch Gill Hey Nick Jowett Timothy Knowles Ken Massy Saskia Pfrengle Philippe Lefranc Olivier Lemercier Arnaud Lefebvre César Heras Martínez Virginia Galera Olmo Ana Bastida Ramírez Joaquín Lomba Maurandi Tona Majó Jacqueline I McKinley Kathleen McSweeney Balázs Gusztáv Mende Alessandra Modi Gabriella Kulcsár Viktória Kiss András Czene Róbert Patay Anna Endrődi Kitti Köhler Tamás Hajdu Tamás Szeniczey János Dani Zsolt Bernert Maya Hoole Olivia Cheronet Denise Keating Petr Velemínský Miroslav Dobeš Francesca Candilio Fraser Brown Raúl Flores Fernández Ana-Mercedes Herrero-Corral Sebastiano Tusa Emiliano Carnieri Luigi Lentini Antonella Valenti Alessandro Zanini Clive Waddington Germán Delibes Elisa Guerra-Doce Benjamin Neil Marcus Brittain Mike Luke Richard Mortimer Jocelyne Desideri Marie Besse Günter Brücken Mirosław Furmanek Agata Hałuszko Maksym Mackiewicz Artur Rapiński Stephany Leach Ignacio Soriano Katina T Lillios João Luís Cardoso Michael Parker Pearson Piotr Włodarczak T Douglas Price Pilar Prieto Pierre-Jérôme Rey Roberto Risch Manuel A Rojo Guerra Aurore Schmitt Joël Serralongue Ana Maria Silva Václav Smrčka Luc Vergnaud João Zilhão David Caramelli Thomas Higham Mark G Thomas Douglas J Kennett Harry Fokkens Volker Heyd Alison Sheridan Karl-Göran Sjögren Philipp W Stockhammer Johannes Krause Ron Pinhasi Wolfgang Haak Ian Barnes Carles Lalueza-Fox David Reich

Nature 2018 03;555(7697):543

This corrects the article DOI: 10.1038/nature25738.
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http://dx.doi.org/10.1038/nature26164DOI Listing
March 2018

The Beaker phenomenon and the genomic transformation of northwest Europe.

Authors:
Iñigo Olalde Selina Brace Morten E Allentoft Ian Armit Kristian Kristiansen Thomas Booth Nadin Rohland Swapan Mallick Anna Szécsényi-Nagy Alissa Mittnik Eveline Altena Mark Lipson Iosif Lazaridis Thomas K Harper Nick Patterson Nasreen Broomandkhoshbacht Yoan Diekmann Zuzana Faltyskova Daniel Fernandes Matthew Ferry Eadaoin Harney Peter de Knijff Megan Michel Jonas Oppenheimer Kristin Stewardson Alistair Barclay Kurt Werner Alt Corina Liesau Patricia Ríos Concepción Blasco Jorge Vega Miguel Roberto Menduiña García Azucena Avilés Fernández Eszter Bánffy Maria Bernabò-Brea David Billoin Clive Bonsall Laura Bonsall Tim Allen Lindsey Büster Sophie Carver Laura Castells Navarro Oliver E Craig Gordon T Cook Barry Cunliffe Anthony Denaire Kirsten Egging Dinwiddy Natasha Dodwell Michal Ernée Christopher Evans Milan Kuchařík Joan Francès Farré Chris Fowler Michiel Gazenbeek Rafael Garrido Pena María Haber-Uriarte Elżbieta Haduch Gill Hey Nick Jowett Timothy Knowles Ken Massy Saskia Pfrengle Philippe Lefranc Olivier Lemercier Arnaud Lefebvre César Heras Martínez Virginia Galera Olmo Ana Bastida Ramírez Joaquín Lomba Maurandi Tona Majó Jacqueline I McKinley Kathleen McSweeney Balázs Gusztáv Mende Alessandra Modi Gabriella Kulcsár Viktória Kiss András Czene Róbert Patay Anna Endrődi Kitti Köhler Tamás Hajdu Tamás Szeniczey János Dani Zsolt Bernert Maya Hoole Olivia Cheronet Denise Keating Petr Velemínský Miroslav Dobeš Francesca Candilio Fraser Brown Raúl Flores Fernández Ana-Mercedes Herrero-Corral Sebastiano Tusa Emiliano Carnieri Luigi Lentini Antonella Valenti Alessandro Zanini Clive Waddington Germán Delibes Elisa Guerra-Doce Benjamin Neil Marcus Brittain Mike Luke Richard Mortimer Jocelyne Desideri Marie Besse Günter Brücken Mirosław Furmanek Agata Hałuszko Maksym Mackiewicz Artur Rapiński Stephany Leach Ignacio Soriano Katina T Lillios João Luís Cardoso Michael Parker Pearson Piotr Włodarczak T Douglas Price Pilar Prieto Pierre-Jérôme Rey Roberto Risch Manuel A Rojo Guerra Aurore Schmitt Joël Serralongue Ana Maria Silva Václav Smrčka Luc Vergnaud João Zilhão David Caramelli Thomas Higham Mark G Thomas Douglas J Kennett Harry Fokkens Volker Heyd Alison Sheridan Karl-Göran Sjögren Philipp W Stockhammer Johannes Krause Ron Pinhasi Wolfgang Haak Ian Barnes Carles Lalueza-Fox David Reich

Nature 2018 03 21;555(7695):190-196. Epub 2018 Feb 21.

Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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http://dx.doi.org/10.1038/nature25738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973796PMC
March 2018

Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor.

Hypertension 2018 02 11;71(2):273-279. Epub 2017 Dec 11.

From the Department of Biology (L.P.) and Endocrinology Unit, Department of Medicine (F.M.), University of Padova, Italy; Estonian Biocentre, Tartu (L.P.); Research Department of Genetics, Evolution and Environment, University College London, United Kingdom (Y.D., M.G.T.); Department of Biological Geological and Environmental Sciences (M.S., S.D.F., D.L.) and Department of Experimental, Diagnostic and Specialty Medicine (P.G.), University of Bologna, Italy; IRCCS Centro Cardiologico Monzino, Milano, Italy (M.R.); Department of Oncology and Advanced Technologies, Laboratory of Molecular Biology (E.F., B.C.) and Department of Internal Medicine (E.R.), IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy; Department of Endocrinology and Metabolic Diseases, San Raffaele Scientific Institute, Milano, Italy (A.C.); and Department of Molecular Medicine, University of Pavia, Italy (F.N., O.Z.).

Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent. HVRI (the hypervariable region I) of the mitochondrial DNA genome and the Y chromosome short tandem repeats profiles were analyzed in individuals of the 3 families. Genotyping 542 585 genome-wide single nucleotide polymorphisms was performed in all the patients with Liddle syndrome of the 3 families and some of their relatives. A panel of 780 healthy Italian adult samples typed for the same set of markers was used as controls. espite different lineages between the 3 families based on the analysis of mitochondrial DNA and Y chromosome, the 3 probands and their 6 affected relatives share the same ≈5 Mbp long haplotype which encompasses the mutant allele. Using an approach based on coalescent theory, we estimate that the 3 families inherited the mutant allele from a common ancestor ≈13 generations ago and that such an ancestor may have left ≈20 carriers alive today. The prevalence of Liddle syndrome in the region of origin of the 3 families may be much higher than that estimated worldwide.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767121PMC
February 2018

Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans.

Mol Biol Evol 2018 Mar;35(3):623-630

Estonian Biocentre, Tartu, Estonia.

Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans.
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http://dx.doi.org/10.1093/molbev/msx314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850494PMC
March 2018