| 1. |
- Acharya, B. S., et al.
(author)
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Introducing the CTA concept
- 2013
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In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Journal article (other academic/artistic)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 3. |
- Richards, Stephen, et al.
(author)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Journal article (peer-reviewed)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 4. |
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| 5. |
- Astuto, Lisa M., et al.
(author)
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Genetic heterogeneity of Usher syndrome : analysis of 151 families with Usher type 1
- 2000
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 67:6, s. 1569-1574
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Journal article (peer-reviewed)abstract
- Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.
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| 6. |
- Ludwig, Sebastian, et al.
(author)
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Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
- 2023
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In: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
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Journal article (peer-reviewed)abstract
- Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
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| 7. |
- Rizik, David G., et al.
(author)
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Long-term Outcomes of Transcatheter Aortic Valve Replacement With the Lotus Valve vs CoreValve/EvolutR : A Secondary Analysis of the REPRISE III Randomized Clinical Trial
- 2022
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In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:10, s. 1-11
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Journal article (peer-reviewed)abstract
- Importance: Long-term follow-up after transcatheter aortic valve replacement (TAVR) is of interest given that longitudinal data on mortality and durability of transcatheter heart valves are limited. The REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System-Randomized Clinical Evaluation) randomized clinical trial compared the mechanically expanded Lotus valve with the self-expanding CoreValve/EvolutR TAVR platforms. Objective: To describe the final 5-year outcomes of the REPRISE III trial. Design, Setting, and Participants: This prespecified secondary analysis assessed the final 5-year clinical, functional, and echocardiographic outcomes of 912 patients from the REPRISE III trial, which was conducted at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015. Patients had high risk for aortic stenosis or severe or symptomatic aortic stenosis. Data were analyzed from September 22, 2014, to May 21, 2021. Intervention: Lotus valve or CoreValve/EvolutR TAVR platforms. Main Outcomes and Measures: Valve Academic Research Consortium-2 end points, hemodynamic measures, functional status, and health status were examined through the 5-year follow-up. Results: A total of 912 patients (mean [SD] age, 82.8 [7.3] years; 463 women [50.8%]) were randomized to either the Lotus valve group (n = 607) or CoreValve/EvolutR group (n = 305), with a baseline Society of Thoracic Surgeons risk score of 6.8%. Clinical follow-up data from the REPRISE III trial were available for 581 patients (95.7%) in the Lotus valve group and 285 patients (93.4%) in the CoreValve/EvolutR group. At 5 years, the cumulative event rate for all-cause mortality was 50.9% in the Lotus valve group vs 52.8% in the CoreValve/EvolutR group (P = .59). Disabling stroke was less frequent with the Lotus valve vs CoreValve/EvolutR (cumulative event rates, 8.3% vs 12.2%; P = .04), whereas the cumulative event rates for overall stroke were similar in both groups (14.1% vs 15.3%; P = .38). Insertion of a new permanent pacemaker (38.9% vs 27.3%; P < .001) and detection of prosthetic aortic valve thrombosis (5.8% vs 1.8%; P = .007) were more common in the Lotus valve group than in the CoreValve/EvolutR group. A smaller proportion of patients who received the Lotus valve experienced valve malpositioning (0% vs 2.6%; P < .001) and required the use of a second valve (1.0% vs 3.8%; P < .001) during the procedure compared with those who received the CoreValve/EvolutR. Compared with the Lotus valve group, the CoreValve/EvolutR group had a significantly lower mean (SD) aortic gradient (7.8 [4.2] mm Hg vs 12.6 [6.7] mm Hg; P < .001) and larger valve areas (1.57 [0.56] cm2 vs 1.42 [0.42] cm2; P = .10). After 5 years, the proportion of patients with moderate or greater paravalvular leak was not significantly higher with the CoreValve/EvolutR than with the Lotus valve (1.9% vs 0%; P = .31); however, the proportion of patients with mild paravalvular leak was higher in the CoreValve/EvolutR group compared with the Lotus valve group (23.1% vs 7.8%; P = .006). Long-term, similar improvements in New York Heart Association class and Kansas City Cardiomyopathy Questionnaire score were observed in both groups. Conclusions and Relevance: The REPRISE III trial found that, at 5 years, the clinical outcomes of the Lotus valve were comparable to those of the CoreValve/EvolutR and that the Lotus valve was safe and effective. Trial Registration: ClinicalTrials.gov Identifier: NCT02202434.
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| 8. |
- Binder, Zev A., et al.
(author)
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Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
- 2018
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
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Journal article (peer-reviewed)abstract
- We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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| 9. |
- Ellingson, Benjamin M., et al.
(author)
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Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma
- 2018
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In: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 20:9, s. 1240-1250
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Journal article (peer-reviewed)abstract
- Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O-6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.
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| 10. |
- Bjursten, Henrik, et al.
(author)
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The safety of introducing a new generation TAVR device : One departments experience from introducing a second generation repositionable TAVR
- 2017
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: In the evolving field of transcatheter aortic valve replacements a new generation of valves have been introduced to clinical practice. With the complexity of the TAVR procedure and the unique aspects of each TAVR device, there is a perceived risk that changing or adding a new valve in a department could lead to a worse outcome for patients, especially during the learning phase. The objective was to study the safety aspect of introducing a second generation repositionable transcatheter valve (Boston Scientific Lotus valve besides Edwards Sapien valve) in a department. Methods: In a retrospective study, 53 patients receiving the Lotus system, and 47 patients receiving the Sapien system over a period of three years were compared for short-term outcome according to VARC-2 definitions and 1-year survival. Results: Outcome in terms VARC-2 criteria for early safety and clinical efficacy, stroke rate, and survival at 30 days and at 1 year were similar. The Lotus valve had less paravalvular leakage, where 90% had none or trace aortic insufficiency as compared to only 48% for the Sapien system. Conclusions: Introduction of a new generation valve can be done with early device success and safety, and without jeopardizing the outcome for patients up to one year. We found no adverse effects by changing valve type and observed improved outcome in terms of lower PVL-rates. Both existing and new centers starting a TAVR program can benefit from the use of a new generation device.
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