| 51. |
- Janko, Matthew, et al.
(author)
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Contemporary Outcomes After Partial Resection of Infected Aortic Grafts
- 2021
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In: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 76, s. 202-210
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed.RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01)CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.
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| 52. |
- Janko, Matthew R., et al.
(author)
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In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas
- 2021
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In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 73:1, s. 210-221.e1
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Journal article (peer-reviewed)abstract
- Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10-months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population. (J Vasc Surg 2021;73:210-21.)
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| 53. |
- Janko, Matthew R., et al.
(author)
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In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement
- 2022
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In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 76:2, s. 546-
-
Journal article (peer-reviewed)abstract
- Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P <.001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P <.001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.
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| 54. |
- Laniel, Dominique, et al.
(author)
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Aromatic hexazine [N6]4− anion featured in the complex structure of the high-pressure potassium nitrogen compound K9N56
- 2023
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In: Nature Chemistry. - : NATURE PORTFOLIO. - 1755-4330 .- 1755-4349. ; 15:5, s. 641-646
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Journal article (peer-reviewed)abstract
- The recent high-pressure synthesis of pentazolates and the subsequent stabilization of the aromatic [N-5](-) anion at atmospheric pressure have had an immense impact on nitrogen chemistry. Other aromatic nitrogen species have also been actively sought, including the hexaazabenzene N-6 ring. Although a variety of configurations and geometries have been proposed based on ab initio calculations, one that stands out as a likely candidate is the aromatic hexazine anion [N-6](4-). Here we present the synthesis of this species, realized in the high-pressure potassium nitrogen compound K9N56 formed at high pressures (46 and 61 GPa) and high temperature (estimated to be above 2,000 K) by direct reaction between nitrogen and KN3 in a laser-heated diamond anvil cell. The complex structure of K9N56-composed of 520 atoms per unit cell-was solved based on synchrotron single-crystal X-ray diffraction and corroborated by density functional theory calculations. The observed hexazine anion [N-6](4-) is planar and proposed to be aromatic.
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| 55. |
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| 56. |
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| 57. |
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| 58. |
- Mattick, J. S., et al.
(author)
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Long non-coding RNAs: definitions, functions, challenges and recommendations
- 2023
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In: Nature Reviews Molecular Cell Biology. - : Springer Science and Business Media LLC. - 1471-0072 .- 1471-0080. ; 24:6, s. 430-447
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Journal article (peer-reviewed)abstract
- Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development. lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease.
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| 59. |
- Morrison, Kathleen D., et al.
(author)
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Mapping past human land use using archaeological data : A new classification for global land use synthesis and data harmonization
- 2021
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4
-
Journal article (peer-reviewed)abstract
- In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.
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| 60. |
- Piatkowski, Bryan T., et al.
(author)
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Draft Metagenome Sequences of the Sphagnum (Peat Moss) Microbiome from Ambient and Warmed Environments across Europe
- 2022
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In: Microbiology Resource Announcements. - : American Society for Microbiology. - 2576-098X. ; 11:10
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Journal article (peer-reviewed)abstract
- We present 49 metagenome assemblies of the microbiome associated with Sphagnum (peat moss) collected from ambient, artificially warmed, and geothermally warmed conditions across Europe. These data will enable further research regarding the impact of climate change on plant-microbe symbiosis, ecology, and ecosystem functioning of northern peatland ecosystems.
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| 61. |
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| 62. |
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| 63. |
- Sexton, Claire E., et al.
(author)
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Novel avenues of tau research
- 2024
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In: Alzheimer's and Dementia. - 1552-5260. ; 20:3, s. 2240-2261
-
Research review (peer-reviewed)abstract
- INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
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| 64. |
- Short, P., et al.
(author)
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The tidal disruption event AT2018hyz-I. Double-peaked emission lines and a flat Balmer decrement
- 2020
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:3, s. 4119-4133
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Journal article (peer-reviewed)abstract
- We present results from spectroscopic observations of AT 2018hyz, a transient discovered by the All-Sky Automated Survey for Supernova survey at an absolute magnitude of M-V similar to -20.2 mag, in the nucleus of a quiescent galaxy with strong Balmer absorption lines. AT 2018hyz shows a blue spectral continuum and broad emission lines, consistent with previous TDE candidates. High cadence follow-up spectra show broad Balmer lines and He I in early spectra, with He II making an appearance after similar to 70-100 d. The Balmer lines evolve from a smooth broad profile, through a boxy, asymmetric double-peaked phase consistent with accretion disc emission, and back to smooth at late times. The Balmer lines are unlike typical active galactic nucleus in that they show a flat Balmer decrement (H alpha/H beta similar to 1.5), suggesting the lines are collisionally excited rather than being produced via photoionization. The flat Balmer decrement together with the complex profiles suggests that the emission lines originate in a disc chromosphere, analogous to those seen in cataclysmic variables. The low optical depth of material due to a possible partial disruption may be what allows us to observe these double-peaked, collisionally excited lines. The late appearance of He II may be due to an expanding photosphere or outflow, or late-time shocks in debris collisions.
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| 65. |
- Solomonidou, A., et al.
(author)
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The chemical composition of impact craters on Titan : I. Implications for exogenic processing
- 2020
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 641
-
Journal article (peer-reviewed)abstract
- We investigate the spectral behavior of nine Titan impact craters in order to constrain their composition. Past studies that have examined the chemical composition of impact craters on Titan have either used qualitative comparisons between craters or combined all craters into a single unit, rather than separating them by geographic location and/or degradation state. Here, we use Visual and Infrared Mapping Spectrometer (VIMS) data and a radiative transfer code to estimate the atmospheric contribution to the data, extract the surface albedos of the impact craters, and constrain their composition by using a library of candidate Titan materials, including essentially water ice, tholin, a dark component, and other possible ices at different grain sizes. Following a general characterization of the impact craters, we study two impact crater subunits, the "crater floor" and the "ejecta blanket". The results show that the equatorial dune craters - Selk, Ksa, Guabonito, and the crater on Santorini Facula - appear to be purely composed of organic material (mainly an unknown dark component). Titan's midlatitude plain craters - Afekan, Soi, and Forseti - along with Menrva and Sinlap, are enriched in water ice within an organic-based mixture. This follows the geographic pattern observed in our previous work with VIMS data, where the uppermost layers of the midlatitude alluvial fans, undifferentiated plains, and labyrinth terrains were found to consist of a mixture of organics and water ice, while the equatorial plains, hummocky terrains, and dunes were found to consist of a mixture of dark material and tholins. Furthermore, we found that the addition of some form of ice improves the fit in the ejecta spectra of Afekan and Sinlap craters. We find no indication for the presence of either NH3 or CO2 ice. Our main results agree with an existing Titan surface evolution scenario, wherein the impact cratering process produces a mixture of organic material and water ice, which is later "cleaned" through fluvial erosion in the midlatitude plains. This cleaning process does not appear to operate in the equatorial regions, which are quickly covered by a thin layer of sand sediment (with the exception of the freshest crater on Titan, Sinlap). Thus, it appears that active processes are working to shape the surface of Titan, and it remains a dynamic world in the present day.
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| 66. |
- Tawil, Rabi, et al.
(author)
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Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial
- 2024
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In: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 23:5, s. 477-486
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Journal article (peer-reviewed)abstract
- Background Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38 alpha MAPK, a regulator of DUX4 expression, and p38 beta MAPK) for the treatment of facioscapulohumeral muscular dystrophy. Methods We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. Findings Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45<middle dot>7 (SD 12<middle dot>5) years. Least squares mean changes from baseline in DUX4driven gene expression did not differ significantly between the losmapimod (0<middle dot>83 [SE 0<middle dot>61]) and placebo (0<middle dot>40 [0<middle dot>65]) groups (difference 0<middle dot>43 [SE 0<middle dot>56; 95% CI -1<middle dot>04 to 1<middle dot>89]; p=0<middle dot>56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drugrelated) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. Interpretation Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy.
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| 67. |
- Wevers, T., et al.
(author)
-
An elliptical accretion disk following the tidal disruption event AT 2020zso
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- Aims. The modelling of spectroscopic observations of tidal disruption events (TDEs) to date suggests that the newly formed accretion disks are mostly quasi-circular. In this work we study the transient event AT 2020zso, hosted by an active galactic nucleus (AGN; as inferred from narrow emission line diagnostics), with the aim of characterising the properties of its newly formed accretion flow.Methods. We classify AT 2020zso as a TDE based on the blackbody evolution inferred from UV/optical photometric observations and spectral line content and evolution. We identify transient, double-peaked Bowen (N III), He I, He II, and Hα emission lines. We model medium-resolution optical spectroscopy of the He II (after careful de-blending of the N III contribution) and Hα lines during the rise, peak, and early decline of the light curve using relativistic, elliptical accretion disk models.Results. We find that the spectral evolution before the peak can be explained by optical depth effects consistent with an outflowing, optically thick Eddington envelope. Around the peak, the envelope reaches its maximum extent (approximately 1015 cm, or ∼3000–6000 gravitational radii for an inferred black hole mass of 5−10 × 105 M⊙) and becomes optically thin. The Hα and He II emission lines at and after the peak can be reproduced with a highly inclined (i = 85 ± 5 degrees), highly elliptical (e = 0.97 ± 0.01), and relatively compact (Rin = several 100 Rg and Rout = several 1000 Rg) accretion disk.Conclusions. Overall, the line profiles suggest a highly elliptical geometry for the new accretion flow, consistent with theoretical expectations of newly formed TDE disks. We quantitatively confirm, for the first time, the high inclination nature of a Bowen (and X-ray dim) TDE, consistent with the unification picture of TDEs, where the inclination largely determines the observational appearance. Rapid line profile variations rule out the binary supermassive black hole hypothesis as the origin of the eccentricity; these results thus provide a direct link between a TDE in an AGN and the eccentric accretion disk. We illustrate for the first time how optical spectroscopy can be used to constrain the black hole spin, through (the lack of) disk precession signatures (changes in inferred inclination). We constrain the disk alignment timescale to > 15 days in AT2020zso, which rules out high black hole spin values (a < 0.8) for MBH ∼ 106 M⊙ and disk viscosity α ≳ 0.1.
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