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Background Using a combination of data from routine surveillance, genomic sequencing, and phylogeographic analysis, we tracked the spread and introduction events of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focusing on a large university community. Methods Here, we sequenced and analyzed 677 high-quality SARS-CoV-2 genomes from positive RNA samples collected from Purdue University students, faculty, and staff who tested positive for the virus between January 2021 and May 2021, comprising an average of 32% of weekly cases across the time frame. Results Our analysis of circulating SARS-CoV-2 variants over time revealed periods when variants of concern (VOC) Alpha (B.1.1.7) and Iota (B.1.526) reached rapid dominance and documented that VOC Gamma (P.1) was increasing in frequency as campus surveillance was ending. Phylodynamic analysis of Gamma genomes from campus alongside a subsampling of >20 000 previously published P.1 genomes revealed 10 independent introductions of this variant into the Purdue community, predominantly from elsewhere in the United States, with introductions from within the state of Indiana and from Illinois, and possibly Washington and New York, suggesting a degree of domestic spread. Conclusions We conclude that a robust and sustained active and passive surveillance program coupled with genomic sequencing during a pandemic offers important insights into the dynamics of pathogen arrival and spread in a campus community and can help guide mitigation measures.

Congeneric parasites are unlikely to specialize on the same tissues of the same host species, likely because of strong multifarious selection against niche overlap. Exceptions where multiple congeneric species overlap on the same tissues may therefore reveal important insights into the ecological factors underlying the origins and maintenance of diversity. Larvae of sunflower maggot flies in genus Strauzia feed on the pith of plants in the family Asteraceae. Although Strauzia tend to be host specialists, some species overlap in their host use. To resolve the origins of host sharing among these specialist flies, we used reduced representation genomic sequencing to infer the first multi-locus phylogeny of genus Strauzia. Our results show that Helianthus tuberosus and Helianthus grosseserratus each host three different fly species, and that the flies co-occurring on a host are not one another’s closest relatives. Though this pattern implies that host sharing is most likely the result of host shifts, these may not be host shifts in the conventional sense of an insect moving onto an entirely new plant. Many hosts of Strauzia belong to a young (1-2 MYA) clade of perennial sunflowers noted for their frequent introgression and hybrid speciation events. In at least one case, flies may have converged upon a host after their respective ancestral host plants hybridized to form a new sunflower species (H. tuberosus). Broadly, we suggest that rapid and recent adaptive introgression and speciation in this group of plants may have instigated the diversification of their phytophagous fly associates, including the convergence of >1 species onto the same shared host plants.

Lineage losses for man's best friend Dogs have been present in North America for at least 9000 years. To better understand how present-day breeds and populations reflect their introduction to the New World, Ní Leathlobhair et al. sequenced the mitochondrial and nuclear genomes of ancient dogs (see the Perspective by Goodman and Karlsson). The earliest New World dogs were not domesticated from North American wolves but likely originated from a Siberian ancestor. Furthermore, these lineages date back to a common ancestor that coincides with the first human migrations across Beringia. This lineage appears to have been mostly replaced by dogs introduced by Europeans, with the primary extant lineage remaining as a canine transmissible venereal tumor. Science , this issue p. 81 ; see also p. 27

In this mixed-methods study, 118 adult adoptees completed an online survey gathering information on (a) reasons for seeking therapy, (b) preferences for therapists, (c) perception of therapists' degree of emphasis on adoption during therapy, and (d) relationship satisfaction with adoptive and birth family members. The participants also completed the Satisfaction With Therapy and Therapist Scale–Revised (STTS-R), Adoptive Identity Questionnaire (AIQ), and Rosenberg Self-Esteem Scale (SES). Findings were that the therapists' adoption competence was the most important factor for adoptees in selecting therapists, adoption-related issues were the most common reason adoptees sought therapy, and adoptees reported being more satisfied with therapy if their therapists placed emphasis on adoption regardless of the amount of attention that was focused on adoption.

Mycobacterium tuberculosis (M.tb) is a globally distributed, obligate pathogen of humans that can be divided into seven clearly defined lineages. An emerging consensus places the origin and global dispersal of M.tb within the past 6,000 years: identifying how the ancestral clone of M.tb spread and differentiated within this timeframe is important for identifying the ecological drivers of the current pandemic. We used Bayesian phylogeographic inference to reconstruct the migratory history of M.tb in Africa and Eurasia and to investigate lineage specific patterns of spread from a geographically diverse sample of 552 M.tb genomes. Applying evolutionary rates inferred with ancient M.tb genome calibration, we estimated the timing of major events in the migratory history of the pathogen. Inferred timings contextualize M.tb dispersal within historical phenomena that altered patterns of connectivity throughout Africa and Eurasia: trans‐Indian Ocean trade in spices and other goods, the Silk Road and its predecessors, the expansion of the Roman Empire, and the European Age of Exploration. We found that Eastern Africa and Southeast Asia have been critical in the dispersal of M.tb. Our results further reveal that M.tb populations have grown through range expansion, as well as in situ, and delineate the independent evolutionary trajectories of bacterial subpopulations underlying the current pandemic.

Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development – PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.

In Europe, the Ixodes ricinus tick is the most important vector of the etiological agents of Lyme borreliosis and several other emerging tick-borne diseases. Because tick-borne pathogens are dependent on their vectors for transmission, understanding the vector population structure is crucial to inform public health research of pathogen dynamics and spread. However, the population structure and dynamics of this important vector species are not well understood as most genetic studies utilize short mitochondrial and nuclear sequences with little diversity. Herein we obtained and analyzed complete mitochondrial genome (hereafter "mitogenome") sequences to better understand the genetic diversity and the population structure of I. ricinus from two long-standing tick-borne disease foci in northern Italy. Complete mitogenomes of 23 I. ricinus ticks were sequenced at high coverage. Out of 23 mitogenome sequences we identified 17 unique haplotypes composed of 244 segregating sites. Phylogenetic reconstruction using 18 complete mitogenome sequences revealed the coexistence of four highly divergent I. ricinus maternal lineages despite the narrow spatial scale over which these samples were obtained (100km). Notably, the estimated coalescence time of the 18 mitogenome haplotypes is ∼427 thousand years ago (95% HPD 330, 540). This divergence between I. ricinus lineages is consistent with the mitochondrial diversity of other arthropod vector species and indicates that long-term I. ricinus populations may have been less structured and larger than previously thought. Thus, this study suggests that a rapid and accurate retrieval of full mitochondrial genomes from this disease vector enables fine-resolution studies of tick intraspecies genetic relationships, population differentiation, and demographic history.

Repeated emergence, not international dissemination, is behind the rise of multidrug-resistant lineage 4 tuberculosis., On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

Background Approximately 10% to 20% of myocardial perfusion imaging (MPI) tests are inappropriate based on professional-society recommendations. The correlation between inappropriate MPI and quality care metrics is not known. Hypothesis Inappropriate MPI will be associated with low achievement of quality care metrics. Methods We conducted a retrospective cross-sectional investigation at a single Veterans Affairs medical center. Myocardial perfusion imaging tests ordered by primary-care clinicians between December 2010 and July 2011 were assessed for appropriateness (by 2009 criteria). Using documentation of the clinical encounter where MPI was ordered, we determined how often quality care metrics were achieved. Results Among 516 MPI patients, 52 (10.1%) were inappropriate and 464 (89.9%) were not inappropriate (either appropriate or uncertain). Hypertension (82.2%), diabetes mellitus (41.3%), and coronary artery disease (41.1%) were common. Glycated hemoglobin levels were lower in the inappropriate MPI cohort (6.6% vs 7.5%; P = 0.04). No difference was observed in the proportion with goal hemoglobin (62.5% vs 46.3% for appropriate/uncertain; P = 0.258). Systolic blood pressure was not different (132 mm Hg vs 135 mm Hg; P = 0.34). Achievement of several other categorical quality metrics was low in both cohorts and no differences were observed. More than 90% of clinicians documented a plan to achieve most metrics. Conclusions Inappropriate MPI is not associated with performance on metrics of quality care. If an association exists, it may be between inappropriate MPI and overly aggressive care. Most clinicians document a plan of care to address failure of quality metrics, suggesting awareness of the problem.

As dogs have traveled with humans to every continent, they can potentially serve as an excellent proxy when studying human migration history. Past genetic studies into the origins of Native American dogs have used portions of the hypervariable region (HVR) of mitochondrial DNA (mtDNA) to indicate that prior to European contact the dogs of Native Americans originated in Eurasia. In this study, we summarize past DNA studies of both humans and dogs to discuss their population histories in the Americas. We then sequenced a portion of the mtDNA HVR of 42 pre-Columbian dogs from three sites located in Illinois, coastal British Columbia, and Colorado, and identify four novel dog mtDNA haplotypes. Next, we analyzed a dataset comprised of all available ancient dog sequences from the Americas to infer the pre-Columbian population history of dogs in the Americas. Interestingly, we found low levels of genetic diversity for some populations consistent with the possibility of deliberate breeding practices. Furthermore, we identified multiple putative founding haplotypes in addition to dog haplotypes that closely resemble those of wolves, suggesting admixture with North American wolves or perhaps a second domestication of canids in the Americas. Notably, initial effective population size estimates suggest at least 1000 female dogs likely existed in the Americas at the time of the first known canid burial, and that population size increased gradually over time before stabilizing roughly 1200 years before present.

Mycobacterium tuberculosis(M.tb) is a globally distributed, obligate pathogen of humans that can be divided into seven clearly defined lineages. Identifying how the ancestral clone ofM.tbspread and differentiated is important for identifying the ecological drivers of the current pandemic. We reconstructedM.tbmigration in Africa and Eurasia, and investigated lineage specific patterns of spread. Applying evolutionary rates inferred with ancientM.tbgenome calibration, we linkM.tbdispersal to historical phenomena that altered patterns of connectivity throughout Africa and Eurasia: trans-Indian Ocean trade in spices and other goods, the Silk Road and its predecessors, the expansion of the Roman Empire and, the European Age of Exploration. We find that Eastern Africa and Southeast Asia have been critical in the dispersal ofM.tb. Our results reveal complex relationships between spatial dispersal and expansion ofM.tbpopulations, and delineate the independent evolutionary trajectories of bacterial sub-populations underlying the current pandemic.

Pregnancy complications are poorly represented in the archeological record, despite their importance in contemporary and ancient societies. While excavating a Byzantine cemetery in Troy, we discovered calcified abscesses among a woman’s remains. Scanning electron microscopy of the tissue revealed ‘ghost cells’, resulting from dystrophic calcification, which preserved ancient maternal, fetal and bacterial DNA of a severe infection, likely chorioamnionitis. Gardnerella vaginalis and Staphylococcus saprophyticus dominated the abscesses. Phylogenomic analyses of ancient, historical, and contemporary data showed that G. vaginalis Troy fell within contemporary genetic diversity, whereas S. saprophyticus Troy belongs to a lineage that does not appear to be commonly associated with human disease today. We speculate that the ecology of S. saprophyticus infection may have differed in the ancient world as a result of close contacts between humans and domesticated animals. These results highlight the complex and dynamic interactions with our microbial milieu that underlie severe maternal infections. DOI: http://dx.doi.org/10.7554/eLife.20983.001, eLife digest Why and how have some bacteria evolved to cause illness in humans? One way to study bacterial evolution is to search for ancient samples of bacteria and use DNA sequencing technology to investigate how modern bacteria have changed from their ancestors. Understanding the evolution process may help researchers to understand how some bacteria become resistant to the antibiotics designed to kill them. Complications that occur during pregnancy, including bacterial infections, have long been a major cause of death for women. Now, Devault, Mortimer et al. have been able to sequence the DNA of bacteria found in tissue collected from a woman buried 800 years ago in a cemetery in Troy. Some of the woman’s tissues had been well preserved because they had calcified (probably as the result of infection), which preserved their structure in a mineralized layer. Two mineralized “nodules” in the body appear to be the remains of abscesses. Some of the human DNA in the nodules came from a male, suggesting that the woman was pregnant with a boy and that the abscesses formed in placental tissue. Sequencing the DNA of the bacteria in the abscess allowed Devault, Mortimer et al. to diagnose the woman’s infection, which was caused by two types of bacteria. One species, called Gardnerella vaginalis, is found in modern pregnancy-related infections. The DNA of the ancient samples was similar to that of modern bacteria. The other bacteria species was an ancient form of Staphylococcus saprophyticus, a type of bacteria that causes urinary tract infections. However, the DNA of the ancient S. saprophyticus bacteria is quite different to that of the bacteria found in modern humans. Instead, their DNA sequence appears more similar to forms of the bacteria that infect currently livestock. As humans lived closely with their livestock at the time the woman lived, her infection may be due to a type of bacteria that passed easily between humans and animals. Overall, the results suggest that the disease-causing properties of bacteria can arise from a wide range of sources. In addition, Devault, Mortimer et al. have demonstrated that certain types of tissue found in archeological remains are a potential gold mine of information about the evolution of bacteria and other microbes found in the human body. DOI: http://dx.doi.org/10.7554/eLife.20983.002

The study of which life history traits primarily affect molecular evolutionary rates is often confounded by the covariance of these traits. Scombroid fishes (billfishes, tunas, barracudas, and their relatives) are unusual in that their mass-specific metabolic rate is positively associated with body size. This study exploits this atypical pattern of trait variation, which allows for direct tests of whether mass-specific metabolic rate or body size is the more important factor of molecular evolutionary rates. We inferred a phylogeny for scombroids from a supermatrix of molecular and morphological characters and used new phylogenetic comparative approaches to assess the associations of body size and mass-specific metabolic rate with substitution rate. As predicted by the body size hypothesis, there is a negative correlation between body size and substitution rate. However, unexpectedly, we also find a negative association between mass-specific metabolic and substitution rates. These relationships are supported by analyses of the total molecular data, separate mitochondrial and nuclear genes, and individual loci, and they are robust to phylogenetic uncertainty. The molecular evolutionary rates of scombroids are primarily tied to body size. This study demonstrates that groups with novel patterns of trait variation can be particularly informative for identifying which life history traits are the primary factors of molecular evolutionary rates.

Bayesian methods have been adopted by anthropologists for their utility in resolving complex questions about human history based on genetic data. The main advantages of Bayesian methods include simple model comparison, presenting results as a summary of probability distributions, and the explicit inclusion of prior information into analyses. In the field of anthropological genetics, for example, implementing Bayesian skyline plots and approximate Bayesian computation is becoming ubiquitous as means to analyze genetic data for the purpose of demographic or historic inference. Correspondingly, there is a critical need for better understanding of the underlying assumptions, proper applications, and limitations of these two methods by the larger anthropological community. Here we review Bayesian skyline plots and approximate Bayesian computation as applied to human demography and provide examples of the application of these methods to anthropological research questions. We also review the two core components of Bayesian demographic analysis: the coalescent and Bayesian inference. Our goal is to describe their basic mechanics in an attempt to demystify them.

A recent study using both mitochondrial DNA (mtDNA) and microsatellite data reported on a population size discrepancy in the eastern tiger salamander where the effective population size (Ne) estimate of the former exceeded that of the latter. That study suggested, among other hypotheses, that homoplasy of microsatellite alleles is responsible for the discrepancy. In this investigation, we report 10 new cases of a similar discrepancy in five species of tuna. These cases derive from our Bayesian inferences using data from Pacific Bluefin Tuna (Thunnus orientalis) and Yellowfin Tuna (Thunnus albacares), as well as from published estimates of genetic diversity for additional populations of Yellowfin Tuna and three other tuna species. Phylogenetic character analyses of inferred genealogies of Pacific Bluefin and Yellowfin Tuna reveal similar reduced levels of mtDNA and microsatellite homoplasy. Thus, the discrepancy between inferred population sizes from mtDNA and microsatellite data in tuna is most likely not an artifact of the chosen mutation models used in the microsatellite analyses, but may reflect behavioral differences between the sexes such as female-biased philopatry and male-biased dispersal. This explanation now warrants critical testing with more local populations of tuna and with other animal and plant groups that have different life histories.

First introduced to Egypt in 2006, H5N1 highly pathogenic avian influenza has resulted in the death of millions of birds and caused over 350 infections and at least 117 deaths in humans. After a decade of viral circulation, outbreaks continue to occur and diffusion mechanisms between poultry farms remain unclear. Using landscape genetics techniques, we identify the distance models most strongly correlated with the genetic relatedness of the viruses, suggesting the most likely methods of viral diffusion within Egyptian poultry. Using 73 viral genetic sequences obtained from infected birds throughout northern Egypt between 2009 and 2015, we calculated the genetic dissimilarity between H5N1 viruses for all eight gene segments. Spatial correlation was evaluated using Mantel tests and correlograms and multiple regression of distance matrices within causal modeling and relative support frameworks. These tests examine spatial patterns of genetic relatedness, and compare different models of distance. Four models were evaluated: Euclidean distance, road network distance, road network distance via intervening markets, and a least-cost path model designed to approximate wild waterbird travel using niche modeling and circuit theory. Samples from backyard farms were most strongly correlated with least cost path distances. Samples from commercial farms were most strongly correlated with road network distances. Results were largely consistent across gene segments. Results suggest wild birds play an important role in viral diffusion between backyard farms, while commercial farms experience human-mediated diffusion. These results can inform avian influenza surveillance and intervention strategies in Egypt.

Background Babesia microti is an emerging tick-borne apicomplexan parasite with increasing geographic range and incidence in the United States. The rapid expansion of B. microti into its current distribution in the northeastern USA has been due to the range expansion of the tick vector, Ixodes scapularis, upon which the causative agent is dependent for transmission to humans. Results To reconstruct the history of B. microti in the continental USA and clarify the evolutionary origin of human strains, we used multiplexed hybrid capture of 25 B. microti isolates obtained from I. scapularis and human blood. Despite low genomic variation compared with other Apicomplexa, B. microti was strongly structured into three highly differentiated genetic clusters in the northeastern USA. Bayesian analyses of the apicoplast genomes suggest that the origin of the current diversity of B. microti in northeastern USA dates back 46 thousand years with a signature of recent population expansion in the last 1000 years. Human-derived samples belonged to two rarely intermixing clusters, raising the possibility of highly divergent infectious phenotypes in humans. Conclusions Our results validate the multiplexed hybrid capture strategy for characterizing genome-wide diversity and relatedness of B. microti from ticks and humans. We find strong population structure in B. microti samples from the Northeast indicating potential barriers to gene flow. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3225-x) contains supplementary material, which is available to authorized users.

We investigated the evolution of 6 genes from the Treponema pallidum repeat (tpr) gene family, which encode potential virulence factors and are assumed to have evolved through gene duplication and gene conversion events. The 6 loci (tprC, D, G, J, I, and K) were sequenced and analyzed in several members of the genus Treponema, including the 3 subspecies of human T. pallidum (T. pallidum subsp. pallidum, pertenue, and endemicum), Treponema paraluiscuniculi (rabbit syphilis), and the unclassified Fribourg-Blanc (simian) isolate. Phylogenetic methods, recombination analysis, and measures of nucleotide diversity were used to investigate the evolutionary history of the tpr genes. Numerous instances of gene conversion were detected by all 3 methods including both homogenizing gene conversion that involved the entire length of the sequence as well as site-specific conversions that affected smaller regions. We determined the relative age and directionality of the gene conversion events whenever possible. Our data are also relevant to a discussion of the evolution of the treponemes themselves. Higher levels of variation exist between the human subspecies than within them, supporting the classification of the human treponemes into 3 subspecies. In contrast to published theories, the divergence and diversity of T. pallidum subsp. pertenue relative to the other subspecies does not support a much older origin of yaws at the emergence of modern human, nor is the level of divergence seen in T. pallidum subsp. pallidum consistent with a very recent (< 500 years) origin of this subspecies. In general, our results demonstrate that intragenomic recombination has played a significant role in the evolution of the studied tpr genes and emphasize that efforts to infer evolutionary history of the treponemes can be complicated if past recombination events are not recognized.

The “Beijing” Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is spreading globally and has been associated with accelerated disease progression and increased antibiotic resistance. Here we performed a phylodynamic reconstruction of one of the L2 sublineages, the central Asian clade (CAC), which has recently spread to western Europe. We find that recent historical events have contributed to the evolution and dispersal of the CAC. Our timing estimates indicate that the clade was likely introduced to Afghanistan during the 1979–1989 Soviet–Afghan war and spread further after population displacement in the wake of the American invasion in 2001. We also find that drug resistance mutations accumulated on a massive scale in Mtb isolates from former Soviet republics after the fall of the Soviet Union, a pattern that was not observed in CAC isolates from Afghanistan. Our results underscore the detrimental effects of political instability and population displacement on tuberculosis control and demonstrate the power of phylodynamic methods in exploring bacterial evolution in space and time.

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery, spreading efficiently via low-dose fecal-oral transmission. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality. Classical approaches have shown that S. sonnei is genetically conserved and clonal. We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage. © 2012 Nature America, Inc. All rights reserved.

Introduction The Physiological & Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) was derived from a heterogeneous general population and has been used successfully as an audit tool to provide risk-adjusted operative mortality rate. The aim of this study was to investigate whether risk-adjusted scoring systems can accurately predict outcomes of colorectal operations done by colorectal and non-colorectal surgeons. Method The study was conducted prospectively on 899 consecutive patients who underwent major elective and emergency colorectal procedures over three years between 2002 and 2004 at University Hospital Coventry and Warwickshire. The outcome parameter was defined as 30-day mortality. The observed mortality was then compared to POSSUM-predicted mortality. Hosmer–Lemeshow and Fisher's Exact test were used to assess statistical significance in outcome between non- and coloproctologists. Results CR-POSSUM was the most accurate predictive model for outcomes of major colorectal operations between surgeons. The overall mortality rate amongst coloproctologists was 7% (5% elective & 13% emergency), whereas the overall mortality was 17% (3% elective & 21% emergency) in non-coloproctologists. Conclusion CR-POSSUM was the better prediction model than POSSUM. Coloproctologists delivered a significantly lower overall mortality, but not in the emergency setting. However, given the few number of elective colorectal resections performed by non-coloproctologists, more cases are required to permit meaningful comparison for the outcomes of major colorectal operations among different surgeons.

Clothing use is an important modern behavior that contributed to the successful expansion of humans into higher latitudes and cold climates. Previous research suggests that clothing use originated anywhere between 40,000 and 3 Ma, though there is little direct archaeological, fossil, or genetic evidence to support more specific estimates. Since clothing lice evolved from head louse ancestors once humans adopted clothing, dating the emergence of clothing lice may provide more specific estimates of the origin of clothing use. Here, we use a Bayesian coalescent modeling approach to estimate that clothing lice diverged from head louse ancestors at least by 83,000 and possibly as early as 170,000 years ago. Our analysis suggests that the use of clothing likely originated with anatomically modern humans in Africa and reinforces a broad trend of modern human developments in Africa during the Middle to Late Pleistocene.

Bluetongue virus (BTV) is a midge-borne member of the genus Orbivirus that causes an eponymous debilitating livestock disease of great agricultural impact and which has expanded into Europe in recent decades. Reassortment among the ten segments comprising the double-stranded (ds) RNA genome of BTV has played an important role in generating the epidemic strains of this virus in Europe. In this study, we investigated the dynamics of BTV genome segment evolution utilizing time-structured data sets of complete sequences from four segments, totalling 290 sequences largely sampled from ruminant hosts. Our analysis revealed that BTV genome segments generally evolve under strong purifying selection and at substitution rates that are generally lower (mean rates of approximately 0.5-7 x 10(-4) nucleotide substitutions per site, per year) than vector-borne positive-sense viruses with single-strand (ss) RNA genomes. These also represent the most robust estimates of the nucleotide substitution rate in a dsRNA virus generated to date. Additionally, we determined that patterns of geographic structure and times to most recent common ancestor differ substantially between each segment, including a relatively recent origin for the diversity of segment 10 within the past millennium. Together, these findings demonstrate the effect of reassortment to decouple the evolutionary dynamics of BTV genome segments.

Although yellow fever has historically been one of the most important viral infections of humans, relatively little is known about the evolutionary processes that shape its genetic diversity. Similarly, there is limited information on the molecular epidemiology of yellow fever virus (YFV) in Africa even though it most likely first emerged on this continent. Through an analysis of complete E gene sequences, including a newly acquired viral collection from Central and West Africa (Senegal, Cameroon, Central African Republic, Cote d'Ivoire, Mali, and Mauritania), we show that YFV exhibits markedly lower rates of evolutionary change than dengue virus, despite numerous biological similarities between these two viruses. From this observation, along with a lack of clock-like evolutionary behavior in YFV, we suggest that vertical transmission, itself characterized by lower replication rates, may play an important role in the evolution of YFV in its enzootic setting. Despite a reduced rate of nucleotide substitution, phylogenetic patterns and estimates of times to common ancestry in YFV still accord well with the dual histories of colonialism and the slave trade, with areas of sylvatic transmission (such as Kedougou, Senegal) acting as enzootic/epidemic foci. Historically, yellow fever has been one of the most important viral infections of humans, causing considerable morbidity and mortality when it encounters a sufficient number and density of susceptible hosts and where the environment facilitates trans- mission by the principal Aedes (Stegomyia) aegypti mosquito vector (2, 26). It was these conditions that enabled the virus to cause regular and debilitating epidemics throughout the Amer- icas during the 18th and 19th centuries. For example, the Philadelphia yellow fever epidemic of 1793 resulted in 17,000 cases and 5,000 deaths, approximately 10% of the total popu- lation. So notorious were the yellow fever epidemics of the Americas that they even drew the attention of Charles Darwin, who speculated that the virus was most likely of African origin (9). Although fewer than 5,000 cases of human yellow fever were reported in Africa and South America during the period 2000 to 2005, these numbers are likely to be large underesti- mates (2), such that yellow fever may still represent a signifi- cant public health threat. Yellow fever is caused by a single-strand positive sense RNA virus (yellow fever virus (YFV)) that belongs to the family Flaviviridae (genus Flavivirus). Although a great deal is known about the basic biology of YFV, including its likely origin (4) and extent of global genetic diversity (11, 24, 29, 30, 41), other aspects of its evolution remain uncertain. These unresolved questions become particularly apparent relative to information about dengue virus (DENV), where gene sequence data are far more abundant. These two viruses are both classified within the genus Flavivirus and possess a transmission cycle that in- volves primates (and perhaps other mammals) (10) and various species of Aedes mosquitoes and an epidemiological history

To determine the origin, phylogenetic relationships, and evolutionary dynamics of rabbit hemorrhagic disease virus (RHDV), we examined 210 partial and complete capsid gene nucleotide sequences. Using a Bayesian Markov chain Monte Carlo approach, we estimated that these sequences evolved at a rate of 3.9 × 10 −4 to 11.9 × 10 −4 nucleotide substitutions per site per year. This rate was consistent across subsets of data, was robust in response to recombination, and casts doubt on the provenance of viral strains isolated from the 1950s to the 1970s, which share strong sequence similarity to modern isolates. Using the same analysis, we inferred that the time to the most recent common ancestor for a joint group of RHDV and rabbit calicivirus sequences was

Microbial pathogens, and viruses in particular, can serve as important complements to traditional genetic markers when investigating the population histories of their human host. The range of mutation rates for DNA viruses suggests that DNA viruses can be useful markers of both recent and ancient events in their host histories. Here, we assess the utility of a well known DNA virus, JC virus (JCV), for investigating human history and demography. Using complete coding viral genomes, we confirm the phylogeographic structure of JCV in populations worldwide and provide coalescent estimates of its evolutionary rate under two alternative models of its history. Using these rate estimates, we compare Bayesian skyline plots of population size changes for JCV to those of its human host as estimated with coding mitochondrial genomes of the latter. These comparisons, when combined with other evidence including a log Bayes Factor model test, show that JCV is evolving rapidly and is therefore tracking the recent history of its human host. These results support the hypothesis that post-World War II societal changes are most likely responsible for the recent demographic patterns observed among different regional JCV populations. In sum, fast evolving DNA viruses, such as JCV, can complement RNA viruses to provide novel insights about the recent history and demography of their human host.

Analysis of complete mitochondrial genome sequences is becoming increasingly common in genetic studies. The availability of full genome datasets enables an analysis of the information content distributed throughout the mitochondrial genome in order to optimize the research design of future evolutionary studies. The goal of our study was to identify informative regions of the human mitochondrial genome using two criteria: (1) accurate reconstruction of a phylogeny and (2) consistent estimates of time to most recent common ancestor (TMRCA). We created two series of datasets by deleting individual genes of varied length and by deleting 10 equal-size fragments throughout the coding region. Phylogenies were statistically compared to the full-coding-region tree, while coalescent methods were used to estimate the TMRCA and associated credible intervals. Individual fragments important for maintaining a phylogeny similar to the full-coding-region tree encompassed bp 577-2122 and 11,399-16,023, including all or part of 12S rRNA, 16S rRNA, ND4, ND5, ND6, and cytb. The control region only tree was the most poorly resolved with the majority of the tree manifest as an unresolved polytomy. Coalescent estimates of TMRCA were less sensitive to removal of any particular fragment(s) than reconstruction of a consistent phylogeny. Overall, we discovered that half the genome, i.e., bp 3669-11,398, could be removed with no significant change in the phylogeny (p(AU)=0.077) while still maintaining overlap of TMRCA 95% credible intervals. Thus, sequencing a contiguous fragment from bp 11,399 through the control region to bp 3668 would create a dataset that optimizes the information necessary for phylogenetic and coalescent analyses and also takes advantage of the wealth of data already available on the control region.

Summary Situated at the furthest northeastern edge of Canada, the island of Newfoundland (approximately 110,000 km 2 ) and Labrador (approximately 295,000 km 2 ) today constitute a province characterized by abundant natural resources but low population density. Both landmasses were covered by the Laurentide ice sheet during the Last Glacial Maximum (18,000 years before present [YBP]); after the glacier retreated, ice patches remained on the island until ca. 9,000 calibrated (cal) YBP [1]. Nevertheless, indigenous peoples, whose ancestors had trekked some 5,000 km from the west coast, arrived approximately 10,000 cal YBP in Labrador and ca. 6,000 cal YBP in Newfoundland [2, 3]. Differential features in material culture indicate at least three settlement episodes by distinct cultural groups, including the Maritime Archaic, Palaeoeskimo, and Beothuk. Newfoundland has remained home to indigenous peoples until present day with only one apparent hiatus (3,400–2,800 YBP). This record suggests abandonment, severe constriction, or local extinction followed by subsequent immigrations from single or multiple source populations, but the specific dynamics and the cultural and biological relationships, if any, among these successive peoples remain enigmatic [4]. By examining the mitochondrial genome diversity and isotopic ratios of 74 ancient remains in conjunction with the archaeological record, we have provided definitive evidence for the genetic discontinuity between the maternal lineages of these populations. This northeastern margin of North America appears to have been populated multiple times by distinct groups that did not share a recent common ancestry, but rather one much deeper in time at the entry point into the continent.

Background: Approximately 10-20% of myocardial perfusion imaging (MPI) is performed for inappropriate indications. Established metrics of quality outpatient care for coronary artery disease (CAD), hypertension, and diabetes mellitus (DM) have similar, or worse, failure rates. The extent to which inappropriate use of MPI is associated with failure to achieve quality care metrics has not been investigated. Methods: We conducted a cross-sectional investigation of MPI performed on outpatients at a single VA medical center between December 2010 and July 2011. Data were gathered from documentation of the visit when the MPI test was ordered, including metrics of quality care for outpatient management of hypertension, DM, CAD, and smoking. Goals of care were selected from established metrics of quality outpatient care. We also assessed whether the clinician documented a plan to bring the metrics to goal. Results: 516 MPI patients were included, 52 (10.1%) inappropriate (I) and 464 (89.9%) appropriate or uncertain (A/U). Hypertension (82.2%), DM (41.3%), CAD (41.1%), and tobacco use (23.1%) were common. No significant differences between A/U and I cases were observed for CAD quality metrics (aspirin use, p=0.22; beta-blocker use, p>0.99; statin use, p>0.99; lipids at goal, p=0.20). While hemoglobin A1c levels were significantly lower for I cases (6.6% versus 7.5% for A/U cases, p=0.04), no difference was observed in the percent of patients at goal (62.5% for I versus 46.3% for A/U, odds ratio [OR] 2.90, 95% confidence interval [CI] 0.55-15.27, p=0.258). Blood pressure at goal (p=0.36) was not different. Use of tobacco was not different between the two groups (23.2% versus 15.7%, p=0.29), and neither was the proportion without tobacco cessation planning (0.65% versus 3.9%, p=0.08) Overall achievement of quality metrics was poor but similar to other reports of these metrics (CAD 44.8%, DM 47.9%, hypertension 73.1%, smoking 77.5%). Most clinicians documented a reason for not achieving, or a plan to achieve the metrics (CAD 95.3%, DM 68.2%, hypertension 90.8%, smoking 99.0%). Conclusion: Overall, the inappropriate use of MPI is not associated with failure to achieve established metrics of quality outpatient care. On the contrary, most clinicians demonstrate awareness of these care deficiencies by documenting either a reason for not achieving, or a plan of care to achieve quality care metrics

Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), is estimated to infect a new host every second. While analyses of genetic data from natural populations of M.tb have emphasized the role of genetic drift in shaping patterns of diversity, the influence of natural selection on this successful pathogen is less well understood. We investigated the effects of natural selection on patterns of diversity in 63 globally extant genomes of M.tb and related pathogenic mycobacteria. We found evidence of strong purifying selection, with an estimated genome-wide selection coefficient equal to −9.5×10−4 (95% CI −1.1×10−3 to −6.8×10−4); this is several orders of magnitude higher than recent estimates for eukaryotic and prokaryotic organisms. We also identified different patterns of variation across categories of gene function. Genes involved in transport and metabolism of inorganic ions exhibited very low levels of non-synonymous polymorphism, equivalent to categories under strong purifying selection (essential and translation-associated genes). The highest levels of non-synonymous variation were seen in a group of transporter genes, likely due to either diversifying selection or local selective sweeps. In addition to selection, we identified other important influences on M.tb genetic diversity, such as a 25-fold expansion of global M.tb populations coincident with explosive growth in human populations (estimated timing 1684 C.E., 95% CI 1620–1713 C.E.). These results emphasize the parallel demographic histories of this obligate pathogen and its human host, and suggest that the dominant effect of selection on M.tb is removal of novel variants, with exceptions in an interesting group of genes involved in transportation and defense. We speculate that the hostile environment within a host imposes strict demands on M.tb physiology, and thus a substantial fitness cost for most new mutations. In this respect, obligate bacterial pathogens may differ from other host-associated microbes such as symbionts., Author Summary Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis (TB), is a highly prevalent pathogen of humans, estimated to infect one-third of the world's population. Previous investigations of M.tb evolution have emphasized the influence of chance events on populations of these bacteria. To understand why this organism is so well adapted to its niche, we sought to characterize the influence of natural selection on M.tb. DNA sequence data from M.tb populations appeared to be strongly influenced by genome-wide selection against deleterious mutations. This type of selection was particularly evident in three functional categories: genes essential for infection (identified in an animal model of TB), genes involved in protein translation, and genes involved in trafficking and metabolism of inorganic ions. By contrast, a fourth category (‘defense’ genes) exhibited high levels of diversity, consistent with selection for advantageous mutations. In addition to effects of selection on M.tb genomic data, we identified the influence of a pronounced recent expansion in M.tb populations, coincident with explosive growth of human populations around the world. Our results suggest that growth of M.tb populations parallels that of its human host population, and that complex influences lead to emergence and maintenance of adaptive traits in M.tb.