Trends in surgical aortic valve replacement in pre- and post-transcatheter aortic valve replacement eras at a structural heart center

BackgroundThe advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras.MethodsFrom January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000–2011, n = 2,426) and post-TAVR era (2012–2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed.ResultsThe median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p < 0.0001). There were more urgent/emergent/salvage SAVRs (38% vs. 24%) and fewer elective SAVRs (63% vs. 76%), (p < 0.0001) in the post-TAVR group. More bioprosthetic valves were implanted in the post-TAVR group (85% vs. 74%, p < 0.0001). Larger aortic valves were implanted (25 vs. 23 mm, p < 0.0001) and more annular enlargements were performed (5.9% vs. 1.6%, p < 0.0001) in the post-TAVR era. Postoperatively, the post-TAVR group had less blood product transfusion (49% vs. 58%, p < 0.0001), renal failure (1.4% vs. 4.3%, p < 0.0001), pneumonia (2.3% vs. 3.8%, p = 0.01), shorter lengths of stay, and lower in-hospital mortality (1.5% vs. 3.3%, p = 0.0007).ConclusionThe approval of TAVR changed the landscape of aortic valve disease management. At a quaternary academic cardiac surgery center with a well-established structural heart program, patients undergoing isolated SAVR in the post-TAVR era had lower STS PROM, more implantation of bioprosthetic valves, utilization of larger valves, annular enlargement, and lower in-hospital mortality. Isolated SAVR continues to be performed in the TAVR era with excellent outcomes. SAVR remains an essential tool in the lifetime management of aortic valve disease

EST Analysis of Ostreococcus lucimarinus, the Most Compact Eukaryotic Genome, Shows an Excess of Introns in Highly Expressed Genes

Background: The genome of the pico-eukaryotic (bacterial-sized) prasinophyte green alga Ostreococcus lucimarinus has one of the highest gene densities known in eukaryotes, yet it contains many introns. Phylogenetic studies suggest this unusually compact genome (13.2 Mb) is an evolutionarily derived state among prasinophytes. The presence of introns in the highly reduced O. lucimarinus genome appears to be in opposition to simple explanations of genome evolution based on unidirectional tendencies, either neutral or selective. Therefore, patterns of intron retention in this species can potentially provide insights into the forces governing intron evolution. Methodology/Principal Findings: Here we studied intron features and levels of expression in O. lucimarinus using expressed sequence tags (ESTs) to annotate the current genome assembly. ESTs were assembled into unigene clusters that were mapped back to the O. lucimarinus Build 2.0 assembly using BLAST and the level of gene expression was inferred from the number of ESTs in each cluster. We find a positive correlation between expression levels and both intron number (R = +0.0893, p =,0.0005) and intron density (number of introns/kb of CDS; R = +0.0753, p =,0.005). Conclusions/Significance: In a species with a genome that has been recently subjected to a great reduction of non-coding DNA, these results imply the existence of selective/functional roles for introns that are principally detectable in highly expressed genes. In these cases, introns are likely maintained by balancing the selective forces favoring their maintenanc

Evolutionary Convergence on Highly-Conserved 3′ Intron Structures in Intron-Poor Eukaryotes and Insights into the Ancestral Eukaryotic Genome

The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3′ consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3′ splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures

Red and Problematic Green Phylogenetic Signals among Thousands of Nuclear Genes from the Photosynthetic and Apicomplexa-Related Chromera velia

The photosynthetic and basal apicomplexan Chromera velia was recently described, expanding the membership of this otherwise nonphotosynthetic group of parasite protists. Apicomplexans are alveolates with secondary plastids of red algal origin, but the evolutionary history of their nuclear genes is still actively discussed. Using deep sequencing of expressed genes, we investigated the phylogenetic affinities of a stringent filtered set of 3,151 expressed sequence tag-contigs by generating clusters with eukaryotic homologs and constructing phylogenetic trees and networks. The phylogenetic positioning of this alveolate alga was determined and sets of phyla-specific proteins extracted. Phylogenetic trees provided conflicting signals, with 444 trees grouping C. velia with the apicomplexans but 354 trees grouping C. velia with the alveolate oyster pathogen Perkinsus marinus, the latter signal being reinforced from the analysis of shared genes and overall sequence similarity. Among the 513 C. velia nuclear genes that reflect a photosynthetic ancestry and for which nuclear homologs were available both from red and green lineages, 263 indicated a red photosynthetic ancestry, whereas 250 indicated a green photosynthetic ancestry. The same 1:1 signal ratio was found among the putative 255 nuclear-encoded plastid proteins identified. This finding of red and green signals for the alveolate mirrors the result observed in the heterokont lineage and supports a common but not necessarily single origin for the plastid in heterokonts and alveolates. The inference of green endosymbiosis preceding red plastid acquisition in these lineages leads to worryingly complicated evolutionary scenarios, prompting the search for other explanations for the green phylogenetic signal and the amount of hosts involved

Key questions for modelling COVID-19 exit strategies

Combinations of intense non-pharmaceutical interventions ('lockdowns') were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i) improve estimation of key epidemiological parameters; ii) understand sources of heterogeneity in populations; iii) focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing

International audienceCurrent sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans

Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance

Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon emissions

Background: Several independent lines of evidence suggest that Amazon forests have provided a significant carbon sink service, and also that the Amazon carbon sink in intact, mature forests may now be threatened as a result of different processes. There has however been no work done to quantify non-land-use-change forest carbon fluxes on a national basis within Amazonia, or to place these national fluxes and their possible changes in the context of the major anthropogenic carbon fluxes in the region. Here we present a first attempt to interpret results from groundbased monitoring of mature forest carbon fluxes in a biogeographically, politically, and temporally differentiated way. Specifically, using results from a large long-term network of forest plots, we estimate the Amazon biomass carbon balance over the last three decades for the different regions and nine nations of Amazonia, and evaluate the magnitude and trajectory of these differentiated balances in relation to major national anthropogenic carbon emissions. Results: The sink of carbon into mature forests has been remarkably geographically ubiquitous across Amazonia, being substantial and persistent in each of the five biogeographic regions within Amazonia. Between 1980 and 2010, it has more than mitigated the fossil fuel emissions of every single national economy, except that of Venezuela. For most nations (Bolivia, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably additionally mitigated all anthropogenic carbon emissions due to Amazon deforestation and other land use change. While the sink has weakened in some regions since 2000, our analysis suggests that Amazon nations which are able to conserve large areas of natural and semi-natural landscape still contribute globally-significant carbon sequestration. Conclusions: Mature forests across all of Amazonia have contributed significantly to mitigating climate change for decades. Yet Amazon nations have not directly benefited from providing this global scale ecosystem service. We suggest that better monitoring and reporting of the carbon fluxes within mature forests, and understanding the drivers of changes in their balance, must become national, as well as international, priorities