The Opisthokonta and the Ecdysozoa May Not Be Clades: Stronger Support for the Grouping of Plant and Animal than for Animal and Fungi and Stronger Support for the Coelomata than Ecdysozoa

In considering the best possible solutions for answering phylogenetic questions from genomic sequences, we have chosen a strategy that we suggest is superior to others that have gone previously. We have ignored multigene families and instead have used single-gene families. This minimizes the inadvertent analysis of paralogs. We have employed strict data controls and have reasoned that if a protein is not capable of recovering the uncontroversial parts of a phylogenetic tree, then why should we use it for the more controversial parts? We have sliced and diced the data in as many ways as possible in order to uncover the signals in that data. Using this strategy, we have tested two controversial hypotheses concerning eukaryotic phylogenetic relationships: the placement of arthropoda and nematodes and the relationships of animals, plants, and fungi. We have constructed phylogenetic trees from 780 single-gene families from 10 completed genomes and amalgamated these into a single supertree. We have also carried out a total evidence analysis on the only universally distributed protein families that can accurately reconstruct the uncontroversial parts of the phylogenetic tree: a total of five families. In doing so, we ignore the majority of single-gene families that are universally distributed as they do not have the appropriate signals to recover the uncontroversial parts of the tree. We have also ignored every protein that has ever been used previously to address this issue, simply because none of them meet our strict criteria. Using these data controls, site stripping, and multiple analyses, 24 out of 26 analyses strongly support the grouping of vertebrates with arthropods (Coelomata hypothesis) and plants with animals. In the other two analyses, the data were ambivalent. The latter finding overturns an 11-year theory of Eukaryotic evolution; the first confirms what has already been said by others. In the light of this new tree, we reanalyze the evolution of intron gain and loss in the rpL14 gene and find that it is much more compatible with the hypothesis presented here than with the Opisthokonta hypothesis

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

The Opisthokonta and the Ecdysozoa May Not Be Clades: Stronger Support for the Grouping of Plant and Animal than for Animal and Fungi and Stronger Support for the Coelomata than Ecdysozoa

In considering the best possible solutions for answering phylogenetic questions from genomic sequences, we have chosen a strategy that we suggest is superior to others that have gone previously. We have ignored multigene families and instead have used single-gene families. This minimizes the inadvertent analysis of paralogs. We have employed strict data controls and have reasoned that if a protein is not capable of recovering the uncontroversial parts of a phylogenetic tree, then why should we use it for the more controversial parts? We have sliced and diced the data in as many ways as possible in order to uncover the signals in that data. Using this strategy, we have tested two controversial hypotheses concerning eukaryotic phylogenetic relationships: the placement of arthropoda and nematodes and the relationships of animals, plants, and fungi. We have constructed phylogenetic trees from 780 single-gene families from 10 completed genomes and amalgamated these into a single supertree. We have also carried out a total evidence analysis on the only universally distributed protein families that can accurately reconstruct the uncontroversial parts of the phylogenetic tree: a total of five families. In doing so, we ignore the majority of single-gene families that are universally distributed as they do not have the appropriate signals to recover the uncontroversial parts of the tree. We have also ignored every protein that has ever been used previously to address this issue, simply because none of them meet our strict criteria. Using these data controls, site stripping, and multiple analyses, 24 out of 26 analyses strongly support the grouping of vertebrates with arthropods (Coelomata hypothesis) and plants with animals. In the other two analyses, the data were ambivalent. The latter finding overturns an 11-year theory of Eukaryotic evolution; the first confirms what has already been said by others. In the light of this new tree, we reanalyze the evolution of intron gain and loss in the rpL14 gene and find that it is much more compatible with the hypothesis presented here than with the Opisthokonta hypothesis

The Opisthokonta and the Ecdysozoa May Not Be Clades: Stronger Support for the Grouping of Plant and Animal than for Animal and Fungi and Stronger Support for the Coelomata than Ecdysozoa

In considering the best possible solutions for answering phylogenetic questions from genomic sequences, we have chosen a strategy that we suggest is superior to others that have gone previously. We have ignored multigene families and instead have used single-gene families. This minimizes the inadvertent analysis of paralogs. We have employed strict data controls and have reasoned that if a protein is not capable of recovering the uncontroversial parts of a phylogenetic tree, then why should we use it for the more controversial parts? We have sliced and diced the data in as many ways as possible in order to uncover the signals in that data. Using this strategy, we have tested two controversial hypotheses concerning eukaryotic phylogenetic relationships: the placement of arthropoda and nematodes and the relationships of animals, plants, and fungi. We have constructed phylogenetic trees from 780 single-gene families from 10 completed genomes and amalgamated these into a single supertree. We have also carried out a total evidence analysis on the only universally distributed protein families that can accurately reconstruct the uncontroversial parts of the phylogenetic tree: a total of five families. In doing so, we ignore the majority of single-gene families that are universally distributed as they do not have the appropriate signals to recover the uncontroversial parts of the tree. We have also ignored every protein that has ever been used previously to address this issue, simply because none of them meet our strict criteria. Using these data controls, site stripping, and multiple analyses, 24 out of 26 analyses strongly support the grouping of vertebrates with arthropods (Coelomata hypothesis) and plants with animals. In the other two analyses, the data were ambivalent. The latter finding overturns an 11-year theory of Eukaryotic evolution; the first confirms what has already been said by others. In the light of this new tree, we reanalyze the evolution of intron gain and loss in the rpL14 gene and find that it is much more compatible with the hypothesis presented here than with the Opisthokonta hypothesis

The Opisthokonta and the Ecdysozoa may not be clades: stronger support for the grouping of plant and animal than for animal and fungi and stronger support for the Coelomata than Ecdysozoa

In considering the best possible solutions for answering phylogenetic questions from genomic sequences, we have chosen a strategy that we suggest is superior to others that have gone previously. We have ignored multigene families and instead have used single-gene families. This minimizes the inadvertent analysis of paralogs. We have employed strict data controls and have reasoned that if a protein is not capable of recovering the uncontroversial parts of a phylogenetic tree, then why should we use it for the more controversial parts? We have sliced and diced the data in as many ways as possible in order to uncover the signals in that data. Using this strategy, we have tested two controversial hypotheses concerning eukaryotic phylogenetic relationships: the placement of arthropoda and nematodes and the relationships of animals, plants, and fungi. We have constructed phylogenetic trees from 780 single-gene families from 10 completed genomes and amalgamated these into a single supertree. We have also carried out a total evidence analysis on the only universally distributed protein families that can accurately reconstruct the uncontroversial parts of the phylogenetic tree: a total of five families. In doing so, we ignore the majority of single-gene families that are universally distributed as they do not have the appropriate signals to recover the uncontroversial parts of the tree. We have also ignored every protein that has ever been used previously to address this issue, simply because none of them meet our strict criteria. Using these data controls, site stripping, and multiple analyses, 24 out of 26 analyses strongly support the grouping of vertebrates with arthropods (Coelomata hypothesis) and plants with animals. In the other two analyses, the data were ambivalent. The latter finding overturns an 11-year theory of Eukaryotic evolution; the first confirms what has already been said by others. In the light of this new tree, we reanalyze the evolution of intron gain and loss in the rpL14 gene and find that it is much more compatible with the hypothesis presented here than with the Opisthokonta hypothesis