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Showing papers by "VU University Amsterdam published in 2021"


Journal ArticleDOI
TL;DR: A broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions.
Abstract: The impacts of COVID-19 on workers and workplaces across the globe have been dramatic. This broad review of prior research rooted in work and organizational psychology, and related fields, is intended to make sense of the implications for employees, teams, and work organizations. This review and preview of relevant literatures focuses on (a) emergent changes in work practices (e.g., working from home, virtual teamwork) and (b) emergent changes for workers (e.g., social distancing, stress, and unemployment). In addition, potential moderating factors (demographic characteristics, individual differences, and organizational norms) are examined given the likelihood that COVID-19 will generate disparate effects. This broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

654 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1428 moreInstitutions (155)
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


Journal ArticleDOI
TL;DR: It is hypothesized that consequent reduction in the frequency of social contacts, personal losses and the experience of general threats in society reduced well-being, which was associated with increased mental health problems and especially emotional loneliness in this pandemic.
Abstract: OBJECTIVES: With the spread of COVID-19, the Netherlands implemented a policy to keep citizens physically distanced. We hypothesize that consequent reduction in the frequency of social contacts, personal losses and the experience of general threats in society reduced well-being. METHODS: Data were collected from 1,679 Dutch community-dwelling participants aged 65 to 102 years old comprising a longitudinal online panel. Social and emotional loneliness and mental health were measured in May 2020, i.e., two months after the implementation of the measures, and earlier in October and November 2019. RESULTS: In this pandemic, not only loneliness of older people increased, but mental health remained roughly stable. The policy measures for physical distancing did not cause much social isolation but personal losses, worries about the pandemic, and a decline in trust in societal institutions were associated with increased mental health problems and especially emotional loneliness. DISCUSSION: The consequences of long-term social isolation and well-being must be closely monitored.

420 citations


Journal ArticleDOI
TL;DR: Although people with depressive, anxiety, or obsessive-compulsive disorders scored higher on all four symptom scales than did individuals without these mental health disorders, both before and during the COVID-19 pandemic, they did not report a greater increase in symptoms during the pandemic.

386 citations


Journal ArticleDOI
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

378 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1692 moreInstitutions (195)
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


Journal ArticleDOI
12 Feb 2021-Science

351 citations


Journal ArticleDOI
Urmo Võsa1, Annique Claringbould2, Annique Claringbould3, Harm-Jan Westra1, Marc Jan Bonder1, Patrick Deelen, Biao Zeng4, Holger Kirsten5, Ashis Saha6, Roman Kreuzhuber7, Roman Kreuzhuber8, Roman Kreuzhuber3, Seyhan Yazar9, Harm Brugge1, Roy Oelen1, Dylan H. de Vries1, Monique G. P. van der Wijst1, Silva Kasela10, Natalia Pervjakova10, Isabel Alves11, Marie-Julie Favé11, Mawusse Agbessi11, Mark W. Christiansen12, Rick Jansen13, Ilkka Seppälä, Lin Tong14, Alexander Teumer15, Katharina Schramm16, Gibran Hemani17, Joost Verlouw18, Hanieh Yaghootkar19, Hanieh Yaghootkar20, Hanieh Yaghootkar21, Reyhan Sönmez Flitman22, Reyhan Sönmez Flitman23, Andrew A. Brown24, Andrew A. Brown25, Viktorija Kukushkina10, Anette Kalnapenkis10, Sina Rüeger22, Eleonora Porcu22, Jaanika Kronberg10, Johannes Kettunen, Bernett Lee26, Futao Zhang27, Ting Qi27, Jose Alquicira Hernandez9, Wibowo Arindrarto28, Frank Beutner5, Peter A C 't Hoen29, Joyce B. J. van Meurs18, Jenny van Dongen13, Maarten van Iterson28, Morris A. Swertz, Julia Dmitrieva30, Mahmoud Elansary30, Benjamin P. Fairfax31, Michel Georges30, Bastiaan T. Heijmans28, Alex W. Hewitt32, Mika Kähönen, Yungil Kim33, Yungil Kim6, Julian C. Knight31, Peter Kovacs5, Knut Krohn5, Shuang Li1, Markus Loeffler5, Urko M. Marigorta4, Urko M. Marigorta34, Hailang Mei28, Yukihide Momozawa30, Martina Müller-Nurasyid16, Matthias Nauck15, Michel G. Nivard35, Brenda W.J.H. Penninx13, Jonathan K. Pritchard36, Olli T. Raitakari37, Olli T. Raitakari38, Olaf Rötzschke26, Eline Slagboom28, Coen D.A. Stehouwer39, Michael Stumvoll5, Patrick F. Sullivan40, Joachim Thiery5, Anke Tönjes5, Jan H. Veldink41, Uwe Völker15, Robert Warmerdam1, Cisca Wijmenga1, Morris Swertz, Anand Kumar Andiappan26, Grant W. Montgomery27, Samuli Ripatti42, Markus Perola43, Zoltán Kutalik22, Emmanouil T. Dermitzakis24, Emmanouil T. Dermitzakis23, Sven Bergmann23, Sven Bergmann22, Timothy M. Frayling19, Holger Prokisch44, Habibul Ahsan14, Brandon L. Pierce14, Terho Lehtimäki, Dorret I. Boomsma13, Bruce M. Psaty12, Sina A. Gharib12, Philip Awadalla11, Lili Milani10, Willem H. Ouwehand45, Willem H. Ouwehand8, Willem H. Ouwehand7, Kate Downes7, Kate Downes8, Oliver Stegle46, Oliver Stegle3, Alexis Battle6, Peter M. Visscher27, Jian Yang27, Jian Yang47, Markus Scholz5, Joseph E. Powell9, Joseph E. Powell48, Greg Gibson4, Tõnu Esko10, Lude Franke1 
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.

344 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1335 moreInstitutions (144)
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.

320 citations



Journal ArticleDOI
26 Aug 2021
TL;DR: This Primer provides an introduction to genome-wide association studies (GWAS), techniques for deriving functional inferences from the results and applications of GWAS in understanding disease risk and trait architecture, and discusses important ethical considerations when considering GWAS populations and data.
Abstract: Genome-wide association studies (GWAS) test hundreds of thousands of genetic variants across many genomes to find those statistically associated with a specific trait or disease. This methodology has generated a myriad of robust associations for a range of traits and diseases, and the number of associated variants is expected to grow steadily as GWAS sample sizes increase. GWAS results have a range of applications, such as gaining insight into a phenotype’s underlying biology, estimating its heritability, calculating genetic correlations, making clinical risk predictions, informing drug development programmes and inferring potential causal relationships between risk factors and health outcomes. In this Primer, we provide the reader with an introduction to GWAS, explaining their statistical basis and how they are conducted, describe state-of-the art approaches and discuss limitations and challenges, concluding with an overview of the current and future applications for GWAS results. Uffelmann et al. describe the key considerations and best practices for conducting genome-wide association studies (GWAS), techniques for deriving functional inferences from the results and applications of GWAS in understanding disease risk and trait architecture. The Primer also provides information on the best practices for data sharing and discusses important ethical considerations when considering GWAS populations and data.

Journal ArticleDOI
Alexander Kurilshikov1, Carolina Medina-Gomez2, Rodrigo Bacigalupe3, Djawad Radjabzadeh2, Jun Wang3, Jun Wang4, Ayse Demirkan5, Ayse Demirkan1, Caroline I. Le Roy6, Juan Antonio Raygoza Garay7, Casey T. Finnicum8, Xingrong Liu9, Daria V. Zhernakova1, Marc Jan Bonder1, Tue H. Hansen10, Fabian Frost11, Malte C. Rühlemann12, Williams Turpin7, Jee-Young Moon13, Han-Na Kim14, Kreete Lüll15, Elad Barkan16, Shiraz A. Shah17, Myriam Fornage18, Joanna Szopinska-Tokov, Zachary D. Wallen19, Dmitrii Borisevich10, Lars Agréus9, Anna Andreasson20, Corinna Bang12, Larbi Bedrani7, Jordana T. Bell6, Hans Bisgaard17, Michael Boehnke21, Dorret I. Boomsma22, Robert D. Burk13, Annique Claringbould1, Kenneth Croitoru7, Gareth E. Davies8, Gareth E. Davies22, Cornelia M. van Duijn23, Cornelia M. van Duijn2, Liesbeth Duijts2, Gwen Falony3, Jingyuan Fu1, Adriaan van der Graaf1, Torben Hansen10, Georg Homuth11, David A. Hughes24, Richard G. IJzerman25, Matthew A. Jackson23, Matthew A. Jackson6, Vincent W. V. Jaddoe2, Marie Joossens3, Torben Jørgensen10, Daniel Keszthelyi26, Rob Knight27, Markku Laakso28, Matthias Laudes, Lenore J. Launer29, Wolfgang Lieb12, Aldons J. Lusis30, Ad A.M. Masclee26, Henriette A. Moll2, Zlatan Mujagic26, Qi Qibin13, Daphna Rothschild16, Hocheol Shin14, Søren J. Sørensen10, Claire J. Steves6, Jonathan Thorsen17, Nicholas J. Timpson24, Raul Y. Tito3, Sara Vieira-Silva3, Uwe Völker11, Henry Völzke11, Urmo Võsa1, Kaitlin H Wade24, Susanna Walter31, Kyoko Watanabe22, Stefan Weiss11, Frank Ulrich Weiss11, Omer Weissbrod32, Harm-Jan Westra1, Gonneke Willemsen22, Haydeh Payami19, Daisy Jonkers26, Alejandro Arias Vasquez33, Eco J. C. de Geus22, Katie A. Meyer34, Jakob Stokholm17, Eran Segal16, Elin Org15, Cisca Wijmenga1, Hyung Lae Kim35, Robert C. Kaplan36, Tim D. Spector6, André G. Uitterlinden2, Fernando Rivadeneira2, Andre Franke12, Markus M. Lerch11, Lude Franke1, Serena Sanna37, Serena Sanna1, Mauro D'Amato, Oluf Pedersen10, Andrew D. Paterson7, Robert Kraaij2, Jeroen Raes3, Alexandra Zhernakova1 
TL;DR: In this article, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts) and found high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples.
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

Journal ArticleDOI
Eirini Karyotaki1, Eirini Karyotaki2, Eirini Karyotaki3, Orestis Efthimiou4, Orestis Efthimiou3, Clara Miguel2, Clara Miguel5, Frederic Maas genannt Bermpohl6, Toshi A. Furukawa6, Toshi A. Furukawa7, Pim Cuijpers2, Pim Cuijpers5, Heleen Riper5, Heleen Riper2, Vikram Patel1, Adriana Mira, Alan W Gemmil, Albert Yeung1, Alfred Lange8, Alishia D. Williams9, Andrew Mackinnon9, Andrew Mackinnon10, Anna C. M. Geraedts, Annemieke van Straten2, Annemieke van Straten5, Björn Meyer11, Cecilia Björkelund12, Christine Knaevelsrud13, Christopher G. Beevers14, Cristina Botella15, Cristina Botella16, Daniel R. Strunk17, David C. Mohr18, David Daniel Ebert19, David Kessler20, David Kessler21, Derek Richards22, Elizabeth Littlewood23, Erik Forsell24, Fan Feng1, Fang Wang25, Gerhard Andersson24, Gerhard Andersson26, Heather D. Hadjistavropoulos27, Heleen Christensen9, Iony D. Ezawa17, Isabella Choi28, Isabelle M. Rosso29, Isabelle M. Rosso1, Jan Philipp Klein30, Jason Shumake14, Javier García-Campayo31, Jeannette Milgrom, Jessica Smith32, Jesus Montero-Marin4, Jill M. Newby9, Juana Bretón-López16, Juana Bretón-López15, Justine Schneider33, Kristofer Vernmark26, Lara Bücker34, Lisa Sheeber35, Lisanne Warmerdam, Louise Farrer36, Manuel Heinrich13, Marcus J.H. Huibers5, Marcus J.H. Huibers2, Marie Kivi12, Martin Kraepelien24, Nicholas R. Forand37, Nicholas R. Forand38, Nicky Pugh27, Nils Lindefors24, Ove Lintvedt, Pavle Zagorscak13, Per Carlbring39, Rachel Phillips32, Robert Johansson39, Ronald C. Kessler1, Sally Brabyn, Sarah Perini, Scott L. Rauch29, Simon Gilbody40, Simon Gilbody23, Steffen Moritz34, Thomas Berger3, Victor J M Pop41, Viktor Kaldo24, Viktor Kaldo42, Viola Spek41, Yvonne Forsell24 
TL;DR: In this article, the authors conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD-network meta-regression, and found that both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term.
Abstract: Importance Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures Patient Health Questionnaire–9 (PHQ-9) scores. Results Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, −0.8; 95% CI, −1.4 to −0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.

Journal ArticleDOI
Douglas P Wightman1, Iris E. Jansen1, Jeanne E. Savage1, Alexey A. Shadrin2, Shahram Bahrami2, Shahram Bahrami3, Dominic Holland4, Arvid Rongve5, Sigrid Børte2, Sigrid Børte6, Sigrid Børte3, Bendik S. Winsvold6, Bendik S. Winsvold3, Ole Kristian Drange6, Amy E Martinsen2, Amy E Martinsen3, Amy E Martinsen6, Anne Heidi Skogholt6, Cristen J. Willer7, Geir Bråthen6, Ingunn Bosnes8, Ingunn Bosnes6, Jonas B. Nielsen7, Jonas B. Nielsen9, Jonas B. Nielsen6, Lars G. Fritsche7, Laurent F. Thomas6, Linda M. Pedersen3, Maiken Elvestad Gabrielsen6, Marianne Bakke Johnsen6, Marianne Bakke Johnsen2, Marianne Bakke Johnsen3, Tore Wergeland Meisingset6, Wei Zhou10, Wei Zhou7, Petroula Proitsi11, Angela Hodges11, Richard Dobson, Latha Velayudhan11, Karl Heilbron, Adam Auton, Julia M. Sealock12, Lea K. Davis12, Nancy L. Pedersen13, Chandra A. Reynolds14, Ida K. Karlsson13, Ida K. Karlsson15, Sigurdur H. Magnusson16, Hreinn Stefansson16, Steinunn Thordardottir, Palmi V. Jonsson17, Jon Snaedal, Anna Zettergren18, Ingmar Skoog18, Ingmar Skoog19, Silke Kern19, Silke Kern18, Margda Waern19, Margda Waern18, Henrik Zetterberg, Kaj Blennow18, Kaj Blennow19, Eystein Stordal8, Eystein Stordal6, Kristian Hveem6, John-Anker Zwart2, John-Anker Zwart6, John-Anker Zwart3, Lavinia Athanasiu3, Lavinia Athanasiu2, Per Selnes20, Ingvild Saltvedt6, Sigrid Botne Sando6, Ingun Ulstein3, Srdjan Djurovic5, Srdjan Djurovic3, Tormod Fladby2, Tormod Fladby20, Dag Aarsland21, Dag Aarsland11, Geir Selbæk3, Geir Selbæk2, Stephan Ripke22, Stephan Ripke23, Stephan Ripke10, Kari Stefansson16, Ole A. Andreassen2, Ole A. Andreassen3, Danielle Posthuma24, Danielle Posthuma1 
TL;DR: This paper identified microglia, immune cells and protein catabolism as relevant genes for late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest.
Abstract: Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

Journal ArticleDOI
TL;DR: Using tau-positron emission tomography scans from 1,612 individuals, this paper identified four distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%.
Abstract: Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.

Journal ArticleDOI
TL;DR: In this article, the authors examined the relationship between cultural tightness and COVID-19 case and mortality rates as of Oct 16, 2020, using an ordinary least squares regression.

Journal ArticleDOI
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.


Journal ArticleDOI
TL;DR: A review of the literature and current practice concerning diagnosis and management of chronic thromboembolic pulmonary hypertension (CTEPH) is presented in this article, which is a rare complication of acute pulmonary embolism, either symptomatic or not.
Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels less than 500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions. This Statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH. It represents the first collaboration of the European Respiratory Society (ERS), the International CTEPH Association (ICA) and the European Reference Network (ERN)-Lung in the pulmonary hypertension domain. The Statement summarises current knowledge but does not make formal recommendations for clinical practice.


Journal ArticleDOI
TL;DR: In this paper, the authors provide a comprehensive introduction to knowledge graphs, which have recently garnered significant attention from both industry and academia in scenarios that require exploiting diverse, dynamic, large-scale collections of data.
Abstract: In this article, we provide a comprehensive introduction to knowledge graphs, which have recently garnered significant attention from both industry and academia in scenarios that require exploiting diverse, dynamic, large-scale collections of data. After some opening remarks, we motivate and contrast various graph-based data models, as well as languages used to query and validate knowledge graphs. We explain how knowledge can be represented and extracted using a combination of deductive and inductive techniques. We conclude with high-level future research directions for knowledge graphs.

Journal ArticleDOI
Ji Chen1, Ji Chen2, Cassandra N. Spracklen3, Cassandra N. Spracklen4  +475 moreInstitutions (146)
TL;DR: This paper aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available.
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

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TL;DR: In this article, the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) was compared.
Abstract: Summary Background Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes. Methods In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18–99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test. Findings Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, p Interpretation Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology. Funding US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association.

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TL;DR: In this article, blood-based biomarkers of neurodegeneration, such as neurofilament light chain and glial fibrillary acidic protein, appear to provide information on disease progression and potential for monitoring treatment effects.
Abstract: Summary For many years, blood-based biomarkers for Alzheimer's disease seemed unattainable, but recent results have shown that they could become a reality. Convincing data generated with new high-sensitivity assays have emerged with remarkable consistency across different cohorts, but also independent of the precise analytical method used. Concentrations in blood of amyloid and phosphorylated tau proteins associate with the corresponding concentrations in CSF and with amyloid-PET or tau-PET scans. Moreover, other blood-based biomarkers of neurodegeneration, such as neurofilament light chain and glial fibrillary acidic protein, appear to provide information on disease progression and potential for monitoring treatment effects. Now the question emerges of when and how we can bring these biomarkers to clinical practice. This step would pave the way for blood-based biomarkers to support the diagnosis of, and development of treatments for, Alzheimer's disease and other dementias.

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B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3  +1273 moreInstitutions (140)
TL;DR: In this article, the first and second observing runs of the Advanced LIGO and Virgo detector network were used to obtain the first standard-siren measurement of the Hubble constant (H 0).
Abstract: This paper presents the gravitational-wave measurement of the Hubble constant (H 0) using the detections from the first and second observing runs of the Advanced LIGO and Virgo detector network. The presence of the transient electromagnetic counterpart of the binary neutron star GW170817 led to the first standard-siren measurement of H 0. Here we additionally use binary black hole detections in conjunction with galaxy catalogs and report a joint measurement. Our updated measurement is H 0 = km s−1 Mpc−1 (68.3% of the highest density posterior interval with a flat-in-log prior) which is an improvement by a factor of 1.04 (about 4%) over the GW170817-only value of km s−1 Mpc−1. A significant additional contribution currently comes from GW170814, a loud and well-localized detection from a part of the sky thoroughly covered by the Dark Energy Survey. With numerous detections anticipated over the upcoming years, an exhaustive understanding of other systematic effects are also going to become increasingly important. These results establish the path to cosmology using gravitational-wave observations with and without transient electromagnetic counterparts.

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TL;DR: In this article, the effect of pandemic-related confinements on physical activity (PA) levels was examined in a multinational survey performed in 14 countries and found that PA levels have substantially decreased globally during the COVID-19 pandemic.
Abstract: Governments have restricted public life during the COVID-19 pandemic, inter alia closing sports facilities and gyms. As regular exercise is essential for health, this study examined the effect of pandemic-related confinements on physical activity (PA) levels. A multinational survey was performed in 14 countries. Times spent in moderate-to-vigorous physical activity (MVPA) as well as in vigorous physical activity only (VPA) were assessed using the Nordic Physical Activity Questionnaire (short form). Data were obtained for leisure and occupational PA pre- and during restrictions. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). In total, n = 13,503 respondents (39 ± 15 years, 59% females) were surveyed. Compared to pre-restrictions, overall self-reported PA declined by 41% (MVPA) and 42.2% (VPA). Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 80.9% (95% CI: 80.3-81.7) to 62.5% (95% CI: 61.6-63.3). Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic.

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TL;DR: A major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers’ views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.
Abstract: In the context of a recent massive increase in research on plant root functions and their impact on the environment, root ecologists currently face many important challenges to keep on generating cutting-edge, meaningful and integrated knowledge. Consideration of the below-ground components in plant and ecosystem studies has been consistently called for in recent decades, but methodology is disparate and sometimes inappropriate. This handbook, based on the collective effort of a large team of experts, will improve trait comparisons across studies and integration of information across databases by providing standardised methods and controlled vocabularies. It is meant to be used not only as starting point by students and scientists who desire working on below-ground ecosystems, but also by experts for consolidating and broadening their views on multiple aspects of root ecology. Beyond the classical compilation of measurement protocols, we have synthesised recommendations from the literature to provide key background knowledge useful for: (1) defining below-ground plant entities and giving keys for their meaningful dissection, classification and naming beyond the classical fine-root vs coarse-root approach; (2) considering the specificity of root research to produce sound laboratory and field data; (3) describing typical, but overlooked steps for studying roots (e.g. root handling, cleaning and storage); and (4) gathering metadata necessary for the interpretation of results and their reuse. Most importantly, all root traits have been introduced with some degree of ecological context that will be a foundation for understanding their ecological meaning, their typical use and uncertainties, and some methodological and conceptual perspectives for future research. Considering all of this, we urge readers not to solely extract protocol recommendations for trait measurements from this work, but to take a moment to read and reflect on the extensive information contained in this broader guide to root ecology, including sections I-VII and the many introductions to each section and root trait description. Finally, it is critical to understand that a major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers' views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.

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Daniele Paolo Anderle1, V. Bertone2, Xu Cao3, Lei Chang4, Ningbo Chang5, Gu Chen6, Xurong Chen3, Zhuojun Chen7, Zhu-Fang Cui8, Ling-Yun Dai7, Weitian Deng9, Minghui Ding10, Xu Feng11, Chang Gong11, Long-Cheng Gui12, Feng-Kun Guo3, Chengdong Han3, J. J. He13, Tie-Jiun Hou14, Hongxia Huang13, Yin Huang15, Krešimir Kumerički16, L. P. Kaptari3, L. P. Kaptari17, Demin Li18, Hengne Li1, Minxiang Li3, Minxiang Li19, Xue-Qian Li4, Y. T. Liang3, Zuotang Liang20, Chen Liu20, Chuan Liu11, Guoming Liu1, Jie Liu3, Liuming Liu3, X. Liu19, Tiehui Liu20, Xiaofeng Luo21, Zhun Lyu22, Bo-Qiang Ma11, Fu Ma3, Jian-Ping Ma3, Yu-Gang Ma23, Yu-Gang Ma3, Lijun Mao3, C. Mezrag2, Hervé Moutarde2, Jialun Ping13, Si-Xue Qin24, Hang Ren3, Craig D. Roberts8, Juan Rojo25, Guodong Shen3, Chao Shi26, Qintao Song18, Hao Sun27, Paweł Sznajder, Enke Wang1, Fan Wang8, Qian Wang1, Rong Wang3, Ruiru Wang3, Taofeng Wang28, Wei Wang29, Xiaoyu Wang18, Xiaoyun Wang30, Jia-Jun Wu3, Xing-Gang Wu24, Lei Xia31, Bo-Wen Xiao32, Bo-Wen Xiao21, Guoqing Xiao3, Ju Jun Xie3, Ya-Ping Xie3, Hongxi Xing1, Hu-Shan Xu3, Nu Xu21, Nu Xu3, Shu-Sheng Xu33, Mengshi Yan11, Wenbiao Yan31, Wencheng Yan18, Xinhu Yan34, Jiancheng Yang3, Yi Bo Yang3, Zhi Yang35, De-Liang Yao7, Z. Ye36, Pei-Lin Yin33, C.-P. Yuan37, Wenlong Zhan3, Jianhui Zhang38, Jinlong Zhang20, Pengming Zhang39, Yifei Zhang31, Chao Hsi Chang3, Zhenyu Zhang40, Hongwei Zhao3, Kuang Ta Chao11, Qiang Zhao3, Yuxiang Zhao3, Zhengguo Zhao31, Liang Zheng41, Jian Zhou20, Xiang Zhou40, Xiaorong Zhou31, Bing-Song Zou3, Liping Zou3 
TL;DR: In this article, an Electron-ion collider in China (EicC) has been proposed, which will be constructed based on an upgraded heavy-ion accelerator, High Intensity heavy ion Accelerator Facility (HIAF), together with a new electron ring.
Abstract: Lepton scattering is an established ideal tool for studying inner structure of small particles such as nucleons as well as nuclei. As a future high energy nuclear physics project, an Electron-ion collider in China (EicC) has been proposed. It will be constructed based on an upgraded heavy-ion accelerator, High Intensity heavy-ion Accelerator Facility (HIAF) which is currently under construction, together with a new electron ring. The proposed collider will provide highly polarized electrons (with a polarization of ∼80%) and protons (with a polarization of ∼70%) with variable center of mass energies from 15 to 20 GeV and the luminosity of (2–3) × 10$^{33}$ cm$^{−2}$ · s$^{−1}$. Polarized deuterons and Helium-3, as well as unpolarized ion beams from Carbon to Uranium, will be also available at the EicC.The main foci of the EicC will be precision measurements of the structure of the nucleon in the sea quark region, including 3D tomography of nucleon; the partonic structure of nuclei and the parton interaction with the nuclear environment; the exotic states, especially those with heavy flavor quark contents. In addition, issues fundamental to understanding the origin of mass could be addressed by measurements of heavy quarkonia near-threshold production at the EicC. In order to achieve the above-mentioned physics goals, a hermetical detector system will be constructed with cutting-edge technologies.This document is the result of collective contributions and valuable inputs from experts across the globe. The EicC physics program complements the ongoing scientific programs at the Jefferson Laboratory and the future EIC project in the United States. The success of this project will also advance both nuclear and particle physics as well as accelerator and detector technology in China.[graphic not available: see fulltext]

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Richard Sylvester1, Oscar Rodríguez2, Virginia Hernández1, Diana Turturica3, Lenka Bauerová4, Harman Max Bruins1, Harman Max Bruins5, Johannes Bründl6, Theo van der Kwast7, Antonin Brisuda4, José Rubio-Briones, Maximilian Seles8, Anouk E. Hentschel9, Anouk E. Hentschel10, Venkata R.M. Kusuma, Nicolai A. Huebner11, Juliette Cotte12, Laura S. Mertens9, Dimitrios Volanis13, Olivier Cussenot13, Jose D. Subiela Henríquez2, Enrique de la Peña, Francesca Pisano2, Francesca Pisano3, Michael Pešl4, Antoine G. van der Heijden5, Sonja Herdegen6, Alexandre R. Zlotta7, Jaromir Hacek4, Ana Calatrava, Sebastian Mannweiler8, Judith Bosschieter10, David Ashabere, Andrea Haitel11, Jean François Coté12, Soha El Sheikh13, Luca Lunelli12, Ferran Algaba2, Isabel Alemany, Francesco Soria3, Willemien Runneboom5, Johannes Breyer6, Jakko A. Nieuwenhuijzen10, Carlos Llorente, Luca Molinaro3, Christina A. Hulsbergen-van de Kaa5, Matthias Evert6, Lambertus A. Kiemeney5, James N'Dow1, Karin Plass1, Otakar Čapoun4, Otakar Čapoun1, Viktor Soukup1, Viktor Soukup4, J. Domínguez-Escrig1, Daniel Cohen13, Daniel Cohen1, Joan Palou1, Joan Palou2, Paolo Gontero1, Paolo Gontero3, Maximilian Burger6, Maximilian Burger1, Richard Zigeuner8, Richard Zigeuner1, Amir Hugh Mostafid1, Shahrokh F. Shariat4, Shahrokh F. Shariat11, Shahrokh F. Shariat1, Morgan Rouprêt1, Morgan Rouprêt12, Eva Compérat1, Eva Compérat12, Marko Babjuk1, Marko Babjuk4, Marko Babjuk11, Bas W.G. van Rhijn1, Bas W.G. van Rhijn7 
TL;DR: In this paper, the European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT).

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TL;DR: Proponents from multiple sides of the debate describe how their original views have changed in light of recent research, as well as remaining areas of disagreement, to highlight some emerging areas of consensus and provide new directions for future research on attentional capture.
Abstract: For over 25 years, researchers have debated whether physically salient stimuli capture attention in an automatic manner, independent of the observer’s goals, or whether the capture of attention depends on the match between a stimulus and the observer’s task set. Recent evidence suggests an intermediate position in which salient stimuli automatically produce a priority signal, but the capture of attention can be prevented via an inhibitory mechanism that suppresses the salient stimulus. Here, proponents from multiple sides of the debate describe how their original views have changed in light of recent research, as well as remaining areas of disagreement. These perspectives highlight some emerging areas of consensus and provide new directions for future research on attentional capture.