| 1. |
- Geyer, C. E., et al.
(författare)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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| 2. |
- Kennedy, K. M., et al.
(författare)
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Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 613:7945, s. 639-649
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Tidskriftsartikel (refereegranskat)abstract
- Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
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| 3. |
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| 4. |
- Murray, Alison E., et al.
(författare)
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Roadmap for naming uncultivated Archaea and Bacteria
- 2020
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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| 5. |
- Yu, Lei, et al.
(författare)
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Ocean current patterns drive the worldwide colonization of eelgrass (Zostera marina)
- 2023
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Ingår i: Nature Plants. - 2055-026X .- 2055-0278. ; 9:8, s. 1207-1220
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Tidskriftsartikel (refereegranskat)abstract
- Currents are unique drivers of oceanic phylogeography and thus determine the distribution of marine coastal species, along with past glaciations and sea-level changes. Here we reconstruct the worldwide colonization history of eelgrass (Zostera marina L.), the most widely distributed marine flowering plant or seagrass from its origin in the Northwest Pacific, based on nuclear and chloroplast genomes. We identified two divergent Pacific clades with evidence for admixture along the East Pacific coast. Two west-to-east (trans-Pacific) colonization events support the key role of the North Pacific Current. Time-calibrated nuclear and chloroplast phylogenies yielded concordant estimates of the arrival of Z. marina in the Atlantic through the Canadian Arctic, suggesting that eelgrass-based ecosystems, hotspots of biodiversity and carbon sequestration, have only been present there for ~243ky (thousand years). Mediterranean populations were founded ~44kya, while extant distributions along western and eastern Atlantic shores were founded at the end of the Last Glacial Maximum (~19kya), with at least one major refuge being the North Carolina region. The recent colonization and five- to sevenfold lower genomic diversity of the Atlantic compared to the Pacific populations raises concern and opportunity about how Atlantic eelgrass might respond to rapidly warming coastal oceans.
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| 6. |
- Eisen, Katherine E., et al.
(författare)
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Among- and within-population variation in morphology, rewards, and scent in a hawkmoth-pollinated plant
- 2022
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Ingår i: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 109:11, s. 1794-1810
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Tidskriftsartikel (refereegranskat)abstract
- Premise: Floral scent is a complex trait that mediates many plant–insect interactions, but our understanding of how floral scent variation evolves, either independently or in concert with other traits, remains limited. Assessing variation in floral scent at multiple levels of biological organization and comparing patterns of variation in scent to variation in other floral traits can contribute to our understanding of how scent variation evolves in nature. Methods: We used a greenhouse common garden experiment to investigate variation in floral scent at three scales—within plants, among plants, and among populations—and to determine whether scent, alone or in combination with morphology and rewards, contributes to population differentiation in Oenothera cespitosa subsp. marginata. Its range spans most of the biomes in the western United States, such that variation in both the abiotic and biotic environment could contribute to trait variation. Results: Multiple analytical approaches demonstrated substantial variation among and within populations in compound-specific and total floral scent measures. Overall, populations were differentiated in morphology and reward traits and in scent. Across populations, coupled patterns of variation in linalool, leucine-derived compounds, and hypanthium length are consistent with a long-tongued moth pollination syndrome. Conclusions: The considerable variation in floral scent detected within populations suggests that, similar to other floral traits, variation in floral scent may have a heritable genetic component. Differences in patterns of population differentiation in floral scent and in morphology and rewards indicate that these traits may be shaped by different selective pressures.
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| 7. |
- Eisen, Katherine E., et al.
(författare)
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An analytical pipeline to support robust research on the ecology, evolution, and function of floral volatiles
- 2022
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Research on floral volatiles has grown substantially in the last 20 years, which has generated insights into their diversity and prevalence. These studies have paved the way for new research that explores the evolutionary origins and ecological consequences of different types of variation in floral scent, including community-level, functional, and environmentally induced variation. However, to address these types of questions, novel approaches are needed that can handle large sample sizes, provide quality control measures, and make volatile research more transparent and accessible, particularly for scientists without prior experience in this field. Drawing upon a literature review and our own experiences, we present a set of best practices for next-generation research in floral scent. We outline methods for data collection (experimental designs, methods for conducting field collections, analytical chemistry, compound identification) and data analysis (statistical analysis, database integration) that will facilitate the generation and interpretation of quality data. For the intermediate step of data processing, we created the R package bouquet, which provides a data analysis pipeline. The package contains functions that enable users to convert chromatographic peak integrations to a filtered data table that can be used in subsequent statistical analyses. This package includes default settings for filtering out non-floral compounds, including background contamination, based on our best-practice guidelines, but functions and workflows can be easily customized as necessary. Next-generation research into the ecology and evolution of floral scent has the potential to generate broadly relevant insights into how complex traits evolve, their genomic architecture, and their consequences for ecological interactions. In order to fulfill this potential, the methodology of floral scent studies needs to become more transparent and reproducible. By outlining best practices throughout the lifecycle of a project, from experimental design to statistical analysis, and providing an R package that standardizes the data processing pipeline, we provide a resource for new and seasoned researchers in this field and in adjacent fields, where high-throughput and multi-dimensional datasets are common.
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| 8. |
- Hofstede, C., et al.
(författare)
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The Subglacial Lake That Wasn't There : Improved Interpretation From Seismic Data Reveals a Sediment Bedform at Isunnguata Sermia
- 2023
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Ingår i: Journal of Geophysical Research - Earth Surface. - : American Geophysical Union (AGU). - 2169-9003 .- 2169-9011. ; 128:10
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Tidskriftsartikel (refereegranskat)abstract
- Radio Echo Sounding (RES) surveys conducted in May 2010 and April 2011 revealed a 2 km(2) flat area with increased bed reflectivity at the base of Isunnguata Sermia at the western margin of the Greenland Ice Sheet. This flat reflector was located within a localized subglacial hydraulic potential (hydropotential) minimum, as part of a complex and elongated trough system. By analogy with comparable features in Antarctica, the initial interpretation of such a feature was a potential subglacial lake. In September 2013 a co-located seismic survey revealed a 1,750 m by 540 and 37 m thick stratified lens-shaped bedform at the base of a subglacial trough system. Amplitude Versus Angle (AVA) analysis yields a derived reflection coefficient R = 0.09 +/- 0.14 indicative of consolidated sediments possibly overlain by dilatant till. The bed and flank on the northern side of the trough consist of unconsolidated, possibly water-bearing sediments with R = -0.10 +/- 0.08, whereas on the southern side it consists of more consolidated material. We interpret the trough as a key component of the wider subglacial drainage network, for which the sediments on its northern side act as a localized water-storage reservoir. Given the observation of seasonally forming and rapidly draining supraglacial meltwater lakes in this area, we interpret the lens-shaped bedform as deposited by episodically ponding meltwater within the subglacial trough system. Our results highlight the importance of transient subglacial hydrological and sedimentological processes such as drainage events for the interaction of ice sheets and their substrates, to understand ice dynamics in a warming climate. Plain Language Summary A ground based radar survey in West Greenland showed an unusually flat, highly reflective zone in an otherwise rough bed suggesting a possible subglacial lake beneath the ice. The highly reflective zone was part of a drainage system transporting meltwater under the ice sheet. We performed a detailed seismic survey across the area which, unlike radar signals, has the advantage of penetrating through the overlying ice into any rock, sediments and water below it. Analysis of our reflection data reveal that the flat area was in fact an elongated lens-shaped bedform consisting of layered (stratified) sediments. However at a larger angle of incidence, analysis showed the bedform is possibly overlain by a thin layer of water-bearing sediments likely saturated by ponding water. Our interpretation is that episodically draining meltwater from upstream is locally accumulating beneath the ice sheet at this locality, thereby depositing the lens-shaped bedform over many melt seasons.
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| 9. |
- Leray, Matthieu, et al.
(författare)
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Natural experiments and long-term monitoring are critical to understand and predict marine host–microbe ecology and evolution
- 2021
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 19:8, s. e3001322-e3001322
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Tidskriftsartikel (refereegranskat)abstract
- Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host’s physiological capacities; however, the identity and functional role(s) of key members of the microbiome (“core microbiome”) in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems’ capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts’ plastic and adaptive responses to environmental change requires (i) recognizing that individual host–microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.
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| 10. |
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