Showing papers by "Utrecht University published in 2021"
Katholieke Universiteit Leuven1, University of Sheffield2, Medical University of Vienna3, Charité4, University of Bologna5, Vita-Salute San Raffaele University6, University of Manchester7, University of Lugano8, Netherlands Cancer Institute9, Monash University10, St James's University Hospital11, Erasmus University Medical Center12, Aberdeen Royal Infirmary13, University of Aberdeen14, Wrightington, Wigan and Leigh NHS Foundation Trust15, Cardiff University16, University of Amsterdam17, University of Lyon18, Utrecht University19, University of Liverpool20
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa guidelines summarise the most recent findings and advice for their use in clinical practice and include a strong recommendation to consider moderate hypofractionation in intermediate-risk patients.
1,369 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
TL;DR: The SARS-CoV-2 virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection.
Abstract: Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.
802 citations
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, University of Bonn5, German Center for Neurodegenerative Diseases6, Harvard University7, University of Lausanne8, National Research Council9, University of Padua10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Copenhagen27, University of Rochester28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, University of Minho47, Polytechnic Institute of Cávado and Ave48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, I.M. Sechenov First Moscow State Medical University57, Russian Academy of Sciences58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, Ikerbasque65, University of Manchester66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
797 citations
University of Liverpool1, Katholieke Universiteit Leuven2, University of Sheffield3, Medical University of Vienna4, Charité5, University of Bologna6, Vita-Salute San Raffaele University7, Netherlands Cancer Institute8, Monash University9, St James's University Hospital10, Erasmus University Medical Center11, University of Aberdeen12, Aberdeen Royal Infirmary13, Wrightington, Wigan and Leigh NHS Foundation Trust14, Cardiff University15, University of Amsterdam16, University of Lyon17, Utrecht University18
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice and guide the clinician in the discussion with the patient on the treatment decisions to be taken.
561 citations
TL;DR: In this article, the population of 47 compact binary mergers detected with a false-alarm rate of 0.614 were dynamically assembled, and the authors found that the BBH rate likely increases with redshift, but not faster than the star formation rate.
Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.
468 citations
TL;DR: It was showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously.
Abstract: Background University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes—such as sheltering in place during the COVID-19 pandemic—the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion Inadequate efforts to recognize and address college students’ mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.
444 citations
TL;DR: In this article, the authors discuss the structure of mRNA-LNPs, factors that impact their stability, and strategies to optimize them to improve the product stability of COVID-19 vaccines.
428 citations
Guy's and St Thomas' NHS Foundation Trust1, University College London2, University of Bristol3, University Hospitals Bristol NHS Foundation Trust4, University of Paris5, Hebrew University of Jerusalem6, Turku University Hospital7, Ghent University8, Utrecht University9, University of Malaya10, Imperial College London11, University of Oxford12, Harvard University13, Medanta14, Regeneron15, Université Paris-Saclay16, Ministry of Health (Malaysia)17, Genentech18, University Medical Center Groningen19, University of Chicago20, The Queen's Medical Center21, Karolinska University Hospital22, University of Córdoba (Spain)23, Genzyme24, Albert Schweitzer Hospital25, University of British Columbia26, World Health Organization27, University of Toronto28
TL;DR: In this article, a prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
Abstract: Importance Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using theI2statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95];P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92;P Conclusions and Relevance In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration PROSPERO Identifier:CRD42021230155
417 citations
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.
374 citations
TL;DR: In this paper, the authors leveraged a prospective-longitudinal cohort study with data before and during the pandemic to describe patterns of noncompliance with COVID-19 related public health measures in young adults and to identify which characteristics increase the risk of non-compliance.
University Medical Center Groningen1, European Bioinformatics Institute2, Netherlands Cancer Institute3, Georgia Institute of Technology4, Leipzig University5, Johns Hopkins University6, NHS Blood and Transplant7, University of Cambridge8, Garvan Institute of Medical Research9, University of Tartu10, Ontario Institute for Cancer Research11, University of Washington12, Public Health Research Institute13, University of Chicago14, Greifswald University Hospital15, Ludwig Maximilian University of Munich16, University of Bristol17, Erasmus University Rotterdam18, Royal Devon and Exeter Hospital19, University of Westminster20, Luleå University of Technology21, University of Lausanne22, Swiss Institute of Bioinformatics23, University of Geneva24, University of Dundee25, Agency for Science, Technology and Research26, University of Queensland27, Leiden University Medical Center28, Radboud University Nijmegen29, University of Liège30, University of Oxford31, Menzies Research Institute32, Icahn School of Medicine at Mount Sinai33, Ikerbasque34, VU University Amsterdam35, Stanford University36, Turku University Hospital37, University of Turku38, Maastricht University39, Karolinska Institutet40, Utrecht University41, University of Helsinki42, National Institutes of Health43, Technische Universität München44, Wellcome Trust Sanger Institute45, German Cancer Research Center46, Westlake University47, University of New South Wales48
TL;DR: In this article, the authors performed cis-and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium.
Abstract: Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
14 Jan 2021
TL;DR: This Primer on Bayesian statistics summarizes the most important aspects of determining prior distributions, likelihood functions and posterior distributions, in addition to discussing different applications of the method across disciplines.
Abstract: Bayesian statistics is an approach to data analysis based on Bayes’ theorem, where available knowledge about parameters in a statistical model is updated with the information in observed data. The background knowledge is expressed as a prior distribution and combined with observational data in the form of a likelihood function to determine the posterior distribution. The posterior can also be used for making predictions about future events. This Primer describes the stages involved in Bayesian analysis, from specifying the prior and data models to deriving inference, model checking and refinement. We discuss the importance of prior and posterior predictive checking, selecting a proper technique for sampling from a posterior distribution, variational inference and variable selection. Examples of successful applications of Bayesian analysis across various research fields are provided, including in social sciences, ecology, genetics, medicine and more. We propose strategies for reproducibility and reporting standards, outlining an updated WAMBS (when to Worry and how to Avoid the Misuse of Bayesian Statistics) checklist. Finally, we outline the impact of Bayesian analysis on artificial intelligence, a major goal in the next decade. This Primer on Bayesian statistics summarizes the most important aspects of determining prior distributions, likelihood functions and posterior distributions, in addition to discussing different applications of the method across disciplines.
TL;DR: The data recorded by these instruments during their first and second observing runs are described, including the gravitational-wave strain arrays, released as time series sampled at 16384 Hz.
TL;DR: In this article, the authors use a systems framework for studying entrepreneurial ecosystems, develop a measurement instrument of its elements, and use this to compose an entrepreneurial ecosystem index to examine the quality of entrepreneurial ecosystems in the Netherlands.
Abstract: There is a growing interest in ecosystems as an approach for understanding the context of entrepreneurship at the macro level of an organizational community. It consists of all the interdependent actors and factors that enable and constrain entrepreneurship within a particular territory. Although growing in popularity, the entrepreneurial ecosystem concept remains loosely defined and measured. This paper shows the value of taking a systems view of the context of entrepreneurship: understanding entrepreneurial economies from a systems perspective. We use a systems framework for studying entrepreneurial ecosystems, develop a measurement instrument of its elements, and use this to compose an entrepreneurial ecosystem index to examine the quality of entrepreneurial ecosystems in the Netherlands. We find that the prevalence of high-growth firms in a region is strongly related to the quality of its entrepreneurial ecosystem. Strong interrelationships among the ecosystem elements reveal their interdependence and need for a systems perspective.
TL;DR: In this article, the authors estimate that more than 1000 rivers account for 80% of global annual emissions, which range between 0.8 million and 2.7 million metric tons per year, with small urban rivers among the most polluting.
Abstract: Plastic waste increasingly accumulates in the marine environment, but data on the distribution and quantification of riverine sources required for development of effective mitigation are limited. Our model approach includes geographically distributed data on plastic waste, land use, wind, precipitation, and rivers and calculates the probability for plastic waste to reach a river and subsequently the ocean. This probabilistic approach highlights regions that are likely to emit plastic into the ocean. We calibrated our model using recent field observations and show that emissions are distributed over more rivers than previously thought by up to two orders of magnitude. We estimate that more than 1000 rivers account for 80% of global annual emissions, which range between 0.8 million and 2.7 million metric tons per year, with small urban rivers among the most polluting. These high-resolution data allow for the focused development of mitigation strategies and technologies to reduce riverine plastic emissions.
McMaster University1, University of Washington2, United Arab Emirates University3, Copenhagen University Hospital4, St Thomas' Hospital5, University of Michigan6, King Saud bin Abdulaziz University for Health Sciences7, Albert Einstein College of Medicine8, University of Toronto9, Brown University10, Rhode Island Hospital11, Utrecht University12, NewYork–Presbyterian Hospital13, Peking Union Medical College Hospital14, Federal University of São Paulo15, Humanitas University16, University of Ulsan17, National Institutes of Health18, Jagiellonian University Medical College19, Population Health Research Institute20, University of Manitoba21, University at Buffalo22, Homi Bhabha National Institute23, Baylor College of Medicine24, Vanderbilt University25, University of Milano-Bicocca26, King Saud Medical City27, Royal North Shore Hospital28, The George Institute for Global Health29, University of Virginia30, University of Dammam31, Emory University32, University of Pennsylvania33, Agostino Gemelli University Polyclinic34, St George’s University Hospitals NHS Foundation Trust35
TL;DR: The Surviving Sepsis Campaign Coronavirus Diease 2019 (SCCD) 2019 panel as mentioned in this paper provided guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.
Abstract: Background The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. Methods The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. Conclusion The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
TL;DR: It is concluded that systematic approaches to identify the key physicochemical degradation mechanism(s) of formulated mRNA vaccine candidates are currently lacking and rational design of optimally stabilized mRNA vaccine formulations during storage, transport, and administration at refrigerated or ambient temperatures should have top priority in the pharmaceutical development community.
TL;DR: In this paper, the authors synthesize data on the contribution of plant and microbial-derived compounds to stabilized SOM, i.e., aggregates and mineral-associated organic matter (MAOM), and review the role of environmental factors influencing this contribution.
Abstract: Soil organic matter (SOM) represents a major reservoir of stored carbon (C). However, uncertainties regarding the composition and origin of stabilized SOM hinder the implementation of sustainable management strategies. Here, we synthesize data on the contribution of plant- and microbial-derived compounds to stabilized SOM, i.e., aggregates and mineral-associated organic matter (MAOM), and review the role of environmental factors influencing this contribution. Extrapolating amino sugar concentrations in soil based on molecular stoichiometry, we find that microbial necromass accounts for ~50% (agroecosystems) or less (forest ecosystems) of the C stabilized within aggregates and MAOM across studies. This implies that plant biomolecules, including lipids, lignin, and sugars, might account for a substantial portion (≥50%) of the organic matter protected by minerals and aggregates. Indeed, plant-specific sugars and lipids can each account for as much as 10% of organic C within mineral soil fractions, and most reported quantities of plant-specific lipids and lignin in mineral soil fractions are likely underestimates due to irreversible sorption to minerals. A relatively balanced contribution of plant and microbial biomolecules to stabilized SOM in aggregates and MAOM is inconsistent with recent suggestions that stable SOM is comprised mostly of microbial compounds. Land use and soil type appear to profoundly affect the contribution of plant and microbial compounds to stabilized SOM. Consistent with studies of bulk soils, favorable conditions for microbial proliferation in grasslands or fertile Chernozems or Luvisols appear to increase the contribution of microbial compounds, while less favorable conditions for microbial proliferation in forest soils or Podzols/Alisols appear to favor the abundance of plant compounds in stabilized SOM. Combined with a tight link between substrate quality and the abundance of microbial compounds in stabilized SOM, and a potentially inverse relationship between substrate quality and the abundance of plant compounds, these results provide evidence that plant biomolecules might be preferentially stabilized by organo-mineral interactions in some ecosystems. Various areas warrant further research. For example, difficulties in distinguishing direct and indirect effects of temperature and precipitation on the composition of stabilized SOM may be overcome by long-term observational studies that include climate manipulations. Knowledge gaps in the contribution of plant and microbial compounds to stabilized SOM in soil layers below 30 cm depth may simply be closed by extending the sampling depth. Moreover, a refined focus on soil fauna, with potentially strong effects on microbial and plant compounds in stabilized SOM, will provide new insights into SOM dynamics. Future studies should quantify both microbial and plant biomolecules in mineral soil fractions to allow direct comparisons and overcome limitations in existing data. For example, because biomarker-based estimates of microbial-derived C can only indirectly estimate the maximum amount of plant-derived C, exhaustive studies of plant biomarker concentrations could be conducted, including estimates of plant-specific lipids, sugars, and lignin (and biomarkers released following mineral dissolution). Generally, more integrative studies, e.g., combining molecular and isotopic tracers of organic matter inputs with targeted sampling of mineral fractions, are required to improve knowledge of the formation and persistence of stabilized SOM.
University of Maryland, Baltimore County1, University of Arizona2, Utrecht University3, Pennsylvania State University4, University of Queensland5, Max Planck Society6, National University of Cordoba7, University College London8, Northwest University (China)9, University of Maine10, University of Hong Kong11, United Nations Environment Programme12, University of Amsterdam13, Smithsonian Institution14, World Wide Fund for Nature15, Duke University16, Aarhus University17, Wildlife Conservation Society18
TL;DR: In this paper, the authors use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong.
Abstract: Archaeological and paleoecological evidence shows that by 10,000 BCE, all human societies employed varying degrees of ecologically transformative land use practices, including burning, hunting, species propagation, domestication, cultivation, and others that have left long-term legacies across the terrestrial biosphere. Yet, a lingering paradigm among natural scientists, conservationists, and policymakers is that human transformation of terrestrial nature is mostly recent and inherently destructive. Here, we use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong. Even 12,000 y ago, nearly three quarters of Earth’s land was inhabited and therefore shaped by human societies, including more than 95% of temperate and 90% of tropical woodlands. Lands now characterized as “natural,” “intact,” and “wild” generally exhibit long histories of use, as do protected areas and Indigenous lands, and current global patterns of vertebrate species richness and key biodiversity areas are more strongly associated with past patterns of land use than with present ones in regional landscapes now characterized as natural. The current biodiversity crisis can seldom be explained by the loss of uninhabited wildlands, resulting instead from the appropriation, colonization, and intensifying use of the biodiverse cultural landscapes long shaped and sustained by prior societies. Recognizing this deep cultural connection with biodiversity will therefore be essential to resolve the crisis.
TL;DR: This paper discusses three extensions of the RI-CLPM that researchers may be interested in, but are unsure of how to accomplish: including stable, person-level characteristics as predictors and/or outcomes; specifying a multiple-group version; and including multiple indicators.
Abstract: The random intercept cross-lagged panel model (RI-CLPM) is rapidly gaining popularity in psychology and related fields as a structural equation modeling (SEM) approach to longitudinal data. It deco...
Washington University in St. Louis1, Vanderbilt University2, University of California, San Francisco3, University of Washington4, University of Chicago5, University of California, San Diego6, University of Rochester7, Emory University8, Mayo Clinic9, University of Maryland, College Park10, University of California, Los Angeles11, Memorial Sloan Kettering Cancer Center12, Ludwig Maximilian University of Munich13, University of California, Davis14, Utrecht University15, University of Texas MD Anderson Cancer Center16, Harvard University17, Loyola University Chicago18, University of California, Irvine19, University of Rennes20
TL;DR: The pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia remain poor, underlining the need for more effective therapies.
Michigan State University1, International Institute for Applied Systems Analysis2, National Institute for Environmental Studies3, Potsdam Institute for Climate Impact Research4, Humboldt University of Berlin5, University of Nottingham6, Technical University of Crete7, ETH Zurich8, University of Tokyo9, Southern University of Science and Technology10, Cranfield University11, Goethe University Frankfurt12, Vrije Universiteit Brussel13, VU University Amsterdam14, Utrecht University15, East China Normal University16
TL;DR: In this article, using ensemble hydrological simulations, the authors show that climate change could reduce water storage in many regions, especially those in the Southern Hemisphere, and highlight the importance of climate change mitigation to avoid adverse water storage impacts and increased droughts.
Abstract: Terrestrial water storage (TWS) modulates the hydrological cycle and is a key determinant of water availability and an indicator of drought. While historical TWS variations have been increasingly studied, future changes in TWS and the linkages to droughts remain unexamined. Here, using ensemble hydrological simulations, we show that climate change could reduce TWS in many regions, especially those in the Southern Hemisphere. Strong inter-ensemble agreement indicates high confidence in the projected changes that are driven primarily by climate forcing rather than land and water management activities. Declines in TWS translate to increases in future droughts. By the late twenty-first century, the global land area and population in extreme-to-exceptional TWS drought could more than double, each increasing from 3% during 1976–2005 to 7% and 8%, respectively. Our findings highlight the importance of climate change mitigation to avoid adverse TWS impacts and increased droughts, and the need for improved water resource management and adaptation.
Intermountain Healthcare1, Medical College of Wisconsin2, University of Geneva3, University of Iowa4, Utrecht University5, Leiden University Medical Center6, Inova Fairfax Hospital7, University of California, Davis8, UCLA Medical Center9, Ottawa Hospital Research Institute10, Uniformed Services University of the Health Sciences11
TL;DR: The 2nd update to the 9th edition of these guidelines is presented in this article, where the authors provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.
TL;DR: In this paper, the effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied, and the authors randomly assigned patients within 6 weeks.
Abstract: Background The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied. Methods We randomly assigned patients within 6 ho...
TL;DR: In this paper, the authors investigated whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized localized cancer.
Abstract: PURPOSEThis study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized ...
TL;DR: In this article, the safety and economic impacts triggered by poorly understood key processes are identified, such as the formation of corrosive hydrogen sulfide gas, hydrogen loss due to the activity of microbes or permeability changes due to geochemical interactions impacting on the predictability of hydrogen flow through porous media.
Abstract: Expectations for energy storage are high but large-scale underground hydrogen storage in porous media (UHSP) remains largely untested. This article identifies and discusses the scientific challenges of hydrogen storage in porous media for safe and efficient large-scale energy storage to enable a global hydrogen economy. To facilitate hydrogen supply on the scales required for a zero-carbon future, it must be stored in porous geological formations, such as saline aquifers and depleted hydrocarbon reservoirs. Large-scale UHSP offers the much-needed capacity to balance inter-seasonal discrepancies between demand and supply, decouple energy generation from demand and decarbonise heating and transport, supporting decarbonisation of the entire energy system. Despite the vast opportunity provided by UHSP, the maturity is considered low and as such UHSP is associated with several uncertainties and challenges. Here, the safety and economic impacts triggered by poorly understood key processes are identified, such as the formation of corrosive hydrogen sulfide gas, hydrogen loss due to the activity of microbes or permeability changes due to geochemical interactions impacting on the predictability of hydrogen flow through porous media. The wide range of scientific challenges facing UHSP are outlined to improve procedures and workflows for the hydrogen storage cycle, from site selection to storage site operation. Multidisciplinary research, including reservoir engineering, chemistry, geology and microbiology, more complex than required for CH4 or CO2 storage is required in order to implement the safe, efficient and much needed large-scale commercial deployment of UHSP.
TL;DR: In this paper, the diagnosis of periprosthetic joint infection (PJI) can be difficult and all current diagnostic tests have problems with accuracy and interpretation of results, so many new tests have been proposed.
Abstract: Aims The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been propose...