Showing papers by "Trinity College, Dublin published in 2021"
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
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 Rochester27, University of Copenhagen28, 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, Russian Academy of Sciences57, I.M. Sechenov First Moscow State Medical University58, 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
TL;DR: This article found that those resistant to a COVID-19 vaccine were less likely to obtain information about the pandemic from traditional and authoritative sources and had similar levels of mistrust in these sources compared to vaccine accepting respondents.
Abstract: Identifying and understanding COVID-19 vaccine hesitancy within distinct populations may aid future public health messaging. Using nationally representative data from the general adult populations of Ireland (N = 1041) and the United Kingdom (UK; N = 2025), we found that vaccine hesitancy/resistance was evident for 35% and 31% of these populations respectively. Vaccine hesitant/resistant respondents in Ireland and the UK differed on a number of sociodemographic and health-related variables but were similar across a broad array of psychological constructs. In both populations, those resistant to a COVID-19 vaccine were less likely to obtain information about the pandemic from traditional and authoritative sources and had similar levels of mistrust in these sources compared to vaccine accepting respondents. Given the geographical proximity and socio-economic similarity of the populations studied, it is not possible to generalize findings to other populations, however, the methodology employed here may be useful to those wishing to understand COVID-19 vaccine hesitancy elsewhere.
716 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, Columbia University3, National Research University – Higher School of Economics4, Yale University5, University of Lagos6, Institute for Fiscal Studies7, Universidade Nova de Lisboa8, Lahore University of Management Sciences9, University of St Andrews10, Stockholm School of Economics11, Ghent University12, Alternatives13, Trinity College, Dublin14, University of Sierra Leone15, Kathmandu16, Cornell University17, University of Illinois at Chicago18, New York University Abu Dhabi19, Princeton University20, Stockholm University21, Tufts University22, University of Michigan23, Northwestern University24, London School of Economics and Political Science25
TL;DR: In this article, the authors analyzed COVID-19 vaccine acceptance across 15 survey samples covering 10 low and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals.
Abstract: Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
536 citations
TL;DR: The most up-to-date progress on TMN-based nanomaterials is comprehensively reviewed, focusing on geometric-st structure design, electronic-structure engineering, and applications in electrochemical energy conversion and storage, including electrocatalysis, supercapacitors, and rechargeable batteries.
Abstract: Transition metal nitrides (TMNs), by virtue of their unique electronic structure, high electrical conductivity, superior chemical stability, and excellent mechanical robustness, have triggered tremendous research interest over the past decade, and showed great potential for electrochemical energy conversion and storage. However, bulk TMNs usually suffer from limited numbers of active sites and sluggish ionic kinetics, and eventually ordinary electrochemical performance. Designing nanostructured TMNs with tailored morphology and good dispersity has proved an effective strategy to address these issues, which provides a larger specific surface area, more abundant active sites, and shorter ion and mass transport distances over the bulk counterparts. Herein, the most up-to-date progress on TMN-based nanomaterials is comprehensively reviewed, focusing on geometric-structure design, electronic-structure engineering, and applications in electrochemical energy conversion and storage, including electrocatalysis, supercapacitors, and rechargeable batteries. Finally, we outline the future challenges of TMN-based nanomaterials and their possible research directions beyond electrochemical energy applications.
461 citations
Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
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
Trinity College, Dublin1, Haukeland University Hospital2, Uppsala University3, University of Murcia4, Katholieke Universiteit Leuven5, University of Belgrade6, St. George's University7, Aalborg University8, University of Liverpool9, Rhön-Klinikum10, Leipzig University11, University of Modena and Reggio Emilia12, National Yang-Ming University13, Seoul National University Hospital14, Oslo University Hospital15, Yonsei University16, Xi'an Jiaotong-Liverpool University17
322 citations
State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, San Francisco28, University of California, Berkeley29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, Johns Hopkins University62, University of Turin63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.
295 citations
Kazunori Akiyama1, Kazunori Akiyama2, Kazunori Akiyama3, Juan-Carlos Algaba4 +291 more•Institutions (72)
TL;DR: In this article, the authors present a list of authors who have contributed to the work of the authors of this paper: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell
Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gelles, Zachary; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Himwich, Elizabeth; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mus Mejias, Alejandro; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
294 citations
Imperial College London1, Amgen2, University of Zielona Góra3, Medical University of Łódź4, Memorial Hospital of South Bend5, University of Amsterdam6, Opole University7, Leiden University Medical Center8, University of Copenhagen9, Trinity College, Dublin10, Cliniques Universitaires Saint-Luc11, Slovak Medical University12, Magna Græcia University13, University of Gothenburg14, Sahlgrenska University Hospital15, National and Kapodistrian University of Athens16, Charles University in Prague17
TL;DR: In this article, the authors provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement.
Abstract: Aims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. Methods and results An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). Conclusion Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.
277 citations
Harvard University1, VU University Amsterdam2, University of Bern3, University of Oxford4, Public Health Research Institute5, University of Wuppertal6, Kyoto University7, University of Amsterdam8, University of New South Wales9, University of Melbourne10, City University London11, University of Gothenburg12, Free University of Berlin13, University of Texas at Austin14, Carlos III Health Institute15, James I University16, Ohio State University17, Northwestern University18, University of Erlangen-Nuremberg19, University of Bristol20, University Hospitals Bristol NHS Foundation Trust21, Trinity College, Dublin22, University of York23, Karolinska Institutet24, Peking Union Medical College25, Linköping University26, University of Regina27, University of Sydney28, McLean Hospital29, University of Lübeck30, University of Zaragoza31, Imperial College London32, University of Nottingham33, University of Hamburg34, Oregon Research Institute35, Australian National University36, Hofstra University37, The Ohio State University Wexner Medical Center38, Stockholm University39, Hull York Medical School40, Tilburg University41, Linnaeus University42
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.
National Research Council1, University of Twente2, Nottingham Trent University3, Leibniz Association4, University of Piraeus5, Luleå University of Technology6, University of the Basque Country7, Technical University of Madrid8, University of Trento9, Frederick University10, Budapest University of Technology and Economics11, University of Tartu12, Umeå University13, Queen's University Belfast14, Trinity College, Dublin15, Kyushu University16, Academy of Sciences of the Czech Republic17, Aalborg University18, University of Reims Champagne-Ardenne19, Philippine Institute for Development Studies20, Newcastle University21
TL;DR: In this article, the authors present a comparative analysis of the mitigation targets of 327 European cities, as declared in their local climate plans, and analyze whether the type of plan, city size, membership of climate networks, and its regional location are associated with different levels of mitigation ambition.
Abstract: Cities across the globe recognise their role in climate mitigation and are acting to reduce carbon emissions. Knowing whether cities set ambitious climate and energy targets is critical for determining their contribution towards the global 1.5 °C target, partly because it helps to identify areas where further action is necessary. This paper presents a comparative analysis of the mitigation targets of 327 European cities, as declared in their local climate plans. The sample encompasses over 25% of the EU population and includes cities of all sizes across all Member States, plus the UK. The study analyses whether the type of plan, city size, membership of climate networks, and its regional location are associated with different levels of mitigation ambition. Results reveal that 78% of the cities have a GHG emissions reduction target. However, with an average target of 47%, European cities are not on track to reach the Paris Agreement: they need to roughly double their ambitions and efforts. Some cities are ambitious, e.g. 25% of our sample (81) aim to reach carbon neutrality, with the earliest target date being 2020.90% of these cities are members of the Climate Alliance and 75% of the Covenant of Mayors. City size is the strongest predictor for carbon neutrality, whilst climate network(s) membership, combining adaptation and mitigation into a single strategy, and local motivation also play a role. The methods, data, results and analysis of this study can serve as a reference and baseline for tracking climate mitigation ambitions across European and global cities.
McGill University1, Bandim Health Project2, Washington University in St. Louis3, University of Chicago4, Radboud University Nijmegen5, Dresden University of Technology6, University of Melbourne7, Baylor College of Medicine8, Eindhoven University of Technology9, Icahn School of Medicine at Mount Sinai10, University of Cape Town11, Rockefeller University12, Pasteur Institute13, Harvard University14, German Center for Neurodegenerative Diseases15, University of Naples Federico II16, New York University17, Trinity College, Dublin18, National Institutes of Health19, Vanderbilt University20, University of Bonn21, Aix-Marseille University22, University of Southern Denmark23, Cornell University24, Memorial Sloan Kettering Cancer Center25, East Tennessee State University26, Massachusetts Institute of Technology27, Broad Institute28
TL;DR: A common framework is established that describes the experimental standards for defining trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects.
Abstract: The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.
TL;DR: This article examined the role of gold as a hedge or safe-haven asset in different phases of the COVID-19 pandemic crisis, corresponding to the timing of fiscal and monetary stimuli to support the weakened economy.
Kazunori Akiyama1, Kazunori Akiyama2, Kazunori Akiyama3, Juan-Carlos Algaba4 +292 more•Institutions (73)
TL;DR: In this article, the authors present a list of the authors who contributed to the development of this work, including: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A; Bintley, Dan; Bunderwood, Nissim; Bower, Geoffrey C;
Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Freeman, William T.; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mejias, Alejandro Mus; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
University of Oxford1, Trinity College, Dublin2, RWTH Aachen University3, Public Health England4, Beaumont Hospital5, Manchester Royal Infirmary6, China-Japan Friendship Hospital7, University of Bern8, New Generation University College9, Centre for Health Protection10, University of Würzburg11, Royal College of Surgeons in Ireland12, Temple University13, Cardiff University14, Statens Serum Institut15, National Health Laboratory Service16, Pasteur Institute17, Public Health Agency of Canada18, Katholieke Universiteit Leuven19, Karolinska Institutet20, The Chinese University of Hong Kong21, Örebro University22, National Institute for Health and Welfare23, University of Mons24, Public Health Agency of Sweden25, Hospital Sant Joan de Déu Barcelona26, University of Otago27, Israel Ministry of Health28, Korea University29, University of Amsterdam30
TL;DR: In this article, the authors investigated the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic and found that containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in lifethreatening invasive diseases in many countries worldwide.
Abstract: Summary Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27–0·37]) and 82% at 8 weeks (0·18 [0·14–0·23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. Funding Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Publica de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).
TL;DR: Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection as discussed by the authors, which has the capacity to prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.
Abstract: Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection. In principle, the induction of adaptive immunity at mucosal sites, involving secretory antibody responses and tissue-resident T cells, has the capacity to prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms. Although numerous effective mucosal vaccines are in use, the major advances seen with injectable vaccines (including adjuvanted subunit antigens, RNA and DNA vaccines) have not yet been translated into licensed mucosal vaccines, which currently comprise solely live attenuated and inactivated whole-cell preparations. The identification of safe and effective mucosal adjuvants allied to innovative antigen discovery and delivery strategies is key to advancing mucosal vaccines. Significant progress has been made in resolving the mechanisms that regulate innate and adaptive mucosal immunity and in understanding the crosstalk between mucosal sites, and this provides valuable pointers to inform mucosal adjuvant design. In particular, increased knowledge on mucosal antigen-presenting cells, innate lymphoid cell populations and resident memory cells at mucosal sites highlights attractive targets for vaccine design. Exploiting these insights will allow new vaccine technologies to be leveraged to facilitate rational mucosal vaccine design for pathogens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for cancer.
TL;DR: In this article, the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis was evaluated in the Measure Up 1 and Measure Up 2 trials.
TL;DR: SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterized by a ‘cytokine storm’ and lung failure and Vitamin D deficiency has been postulated as a determinant of severity.
Abstract: BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a 'cytokine storm' and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19. METHODS: Narrative review. RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.
TL;DR: In this paper, the authors show that the existence of sharp, dynamic and new correlations between companies related to the term "corona", outside of pre-existing interrelationships.
TL;DR: Recent insights into the influence of PRR activation and inflammasomes on viral infections and what this means for the mammalian host are discussed.
TL;DR: In this paper, a 6-minute walk test (6MWT) was performed on 487 patients with acute SARS-CoV-2 infection at a median of 75 days after diagnosis.
Abstract: Rationale: Much is known about the acute infective process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease (COVID-19) pandemic. The marked inflammatory response and coagulopathic state in acute SARS-CoV-2 infection may promote pulmonary fibrosis. However, little is known about the incidence and seriousness of post-COVID-19 pulmonary pathology. Objectives: To describe the respiratory recovery and self-reported health after infection at the time of outpatient attendance. Methods: Infection severity was graded into three groups: 1) not requiring admission, 2) requiring hospital admission, and 3) requiring intensive care unit care. Participants underwent chest radiography and a 6-minute walk test (6MWT). Fatigue and subjective return to health were assessed, and concentrations of CRP (C-reactive protein), IL-6 (interleukin-6), sCD25 (soluble CD25), and D-dimer were measured. The associations between initial illness and abnormal chest X-ray findings, 6MWT distance, and perception of maximal exertion were investigated. Results: A total of 487 patients were offered an outpatient appointment, of whom 153 (31%) attended for assessment at a median of 75 days after diagnosis. A total of 74 (48%) had required hospital admission during acute infection. Persistently abnormal chest X-ray findings were seen in 4%. The median 6MWT distance covered was 460 m. A reduced distance covered was associated with frailty and length of inpatient stay. A total of 95 (62%) patients believed that they had not returned to full health, whereas 47% met the case definition for fatigue. Ongoing ill health and fatigue were associated with an increased perception of exertion. None of the measures of persistent respiratory disease were associated with initial disease severity. Conclusions: This study highlights the rates of objective respiratory disease and subjective respiratory symptoms after COVID-19 and the complex multifactorial nature of post-COVID-19 ill health.
TL;DR: Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
Abstract: The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesised to represent a measure of biological ageing with a positive/negative residual signifying age acceleration /deceleration respectively. The present study examines the associations of four epigenetic clocks - Horvath, Hannum, PhenoAge, GrimAge - with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). Horvath Age Acceleration (AA) and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
TL;DR: In this paper, the authors assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis, and demonstrate that sustained endotheliopathy was more frequent in older, comorbid patients and those requiring hospitalization.
TL;DR: A public and open digital twin of the Docklands area in Dublin, Ireland is demonstrated and it is shown how this model can be used for urban planning of skylines and green space allowing users to interact and report feedback on planned changes.
TL;DR: In this article, a hydrogel-type shielding material incorporating MXene and poly(acrylic acid) is fabricated through a biomineralization-inspired assembly route, which exhibits excellent stretchability and recyclability, favorable shape adaptability and adhesiveness.
Abstract: The fast development of terahertz technologies demands high-performance electromagnetic interference (EMI) shielding materials to create safe electromagnetic environments. Despite tremendous breakthroughs in achieving superb shielding efficiency (SE), conventional shielding materials have high reflectivity and cannot be re-edited or recycled once formed, resulting in detrimental secondary electromagnetic pollution and poor adaptability. Herein, a hydrogel-type shielding material incorporating MXene and poly(acrylic acid) is fabricated through a biomineralization-inspired assembly route. The composite hydrogel exhibits excellent stretchability and recyclability, favorable shape adaptability and adhesiveness, and fast self-healing capability, demonstrating great application flexibility and reliability. More interestingly, the shielding performance of the hydrogel shows absorption-dominated feature due to the combination of the porous structure, moderate conductivity, and internal water-rich environment. High EMI SE of 45.3 dB and broad effective absorption bandwidth (0.2-2.0 THz) with excellent refection loss of 23.2 dB can be simultaneously achieved in an extremely thin hydrogel (0.13 mm). Furthermore, such hydrogel demonstrates sensitive deformation responses and can be used as an on-skin sensor. This work provides not only an alternative strategy for designing next-generation EMI shielding material but also a highly efficient and convenient method for fabricating MXene composite on macroscopic scales.
TL;DR: This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD, and substantial within-group variance and overlap between groups were observed.
Abstract: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
TL;DR: In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures and the optimal regression model of super-responders versus other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease.
Pacific Northwest National Laboratory1, Lawrence Berkeley National Laboratory2, Trinity College, Dublin3, Argonne National Laboratory4, Oak Ridge National Laboratory5, Ernst Ruska Centre6, Sandia National Laboratories7, National Institute of Standards and Technology8, University of Minnesota9, Virginia Tech10, Johns Hopkins University11
TL;DR: The open, highly integrated and data-driven microscopy architecture needed to realize transformative discoveries in the coming decade is discussed.
Abstract: Electron microscopy touches on nearly every aspect of modern life, underpinning materials development for quantum computing, energy and medicine. We discuss the open, highly integrated and data-driven microscopy architecture needed to realize transformative discoveries in the coming decade.
Newcastle University1, Newcastle upon Tyne Hospitals NHS Foundation Trust2, Bond University3, University of Jaén4, King's College London5, University of Notre Dame Australia6, University of Oxford7, Trinity College, Dublin8, Dalarna University9, Harvard University10, University of Caxias do Sul11, University of Dundee12, Great Ormond Street Hospital13, University of Calgary14, University of Edinburgh15, Esslingen University of Applied Sciences16, University of South Dakota17, Queen Mary University of London18, Imperial College London19, Swansea University20, University of North Dakota21, Icahn School of Medicine at Mount Sinai22, Queensland University of Technology23, University of British Columbia24
TL;DR: The Consensus Statement as mentioned in this paper provides a global, collaborative, representative and inclusive vision for educating an interprofessional healthcare workforce that can deliver sustainably and sustainably care for the patients.
Abstract: The purpose of this Consensus Statement is to provide a global, collaborative, representative and inclusive vision for educating an interprofessional healthcare workforce that can deliver sustainab...