Showing papers by "University of Sydney published in 2021"
TL;DR: It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.
Abstract: Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.
2,705 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
TL;DR: The field of circuit quantum electrodynamics (QED) as discussed by the authors was initiated by Josephson-junction-based superconducting circuits and has become an independent and thriving field of research in its own right.
Abstract: Quantum-mechanical effects at the macroscopic level were first explored in Josephson-junction-based superconducting circuits in the 1980s. In recent decades, the emergence of quantum information science has intensified research toward using these circuits as qubits in quantum information processors. The realization that superconducting qubits can be made to strongly and controllably interact with microwave photons, the quantized electromagnetic fields stored in superconducting circuits, led to the creation of the field of circuit quantum electrodynamics (QED), the topic of this review. While atomic cavity QED inspired many of the early developments of circuit QED, the latter has now become an independent and thriving field of research in its own right. Circuit QED allows the study and control of light-matter interaction at the quantum level in unprecedented detail. It also plays an essential role in all current approaches to gate-based digital quantum information processing with superconducting circuits. In addition, circuit QED provides a framework for the study of hybrid quantum systems, such as quantum dots, magnons, Rydberg atoms, surface acoustic waves, and mechanical systems interacting with microwave photons. Here the coherent coupling of superconducting qubits to microwave photons in high-quality oscillators focusing on the physics of the Jaynes-Cummings model, its dispersive limit, and the different regimes of light-matter interaction in this system are reviewed. Also discussed is coupling of superconducting circuits to their environment, which is necessary for coherent control and measurements in circuit QED, but which also invariably leads to decoherence. Dispersive qubit readout, a central ingredient in almost all circuit QED experiments, is also described. Following an introduction to these fundamental concepts that are at the heart of circuit QED, important use cases of these ideas in quantum information processing and in quantum optics are discussed. Circuit QED realizes a broad set of concepts that open up new possibilities for the study of quantum physics at the macro scale with superconducting circuits and applications to quantum information science in the widest sense.
773 citations
Ben-Gurion University of the Negev1, McMaster University2, Population Health Research Institute3, University of North Carolina at Chapel Hill4, Sanjay Gandhi Post Graduate Institute of Medical Sciences5, University of Gothenburg6, Katholieke Universiteit Leuven7, Iuliu Hațieganu University of Medicine and Pharmacy8, Peking Union Medical College Hospital9, Tohoku University10, University of Sydney11, University of Jos12, Cornell University13, National Autonomous University of Mexico14, University of Manchester15, University of Ghana16, Isfahan University of Medical Sciences17, University of Amsterdam18, Ege University19, Wonkwang University20, Universidade Federal do Rio Grande do Sul21, Pontifical Xavierian University22, Moscow State University of Medicine and Dentistry23, Universiti Sains Malaysia24, Wrocław Medical University25, Dhaka Medical College and Hospital26, Autonomous University of Barcelona27, University of Cape Town28, University of Indonesia29, Queen's University30, National University of Singapore31, Rabin Medical Center32, University of Alberta33, Mazandaran University of Medical Sciences34, Université de Montréal35
TL;DR: It is found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use, and similar trends and relative distributions were found in people who completed internet vs personal interviews.
763 citations
TL;DR: There is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with the pooled odds ratio of 0.56 for being an infected contact compared with adults, although seroprevalence in adolescents appeared similar to adults.
Abstract: Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.
698 citations
TL;DR: Pangolin this paper is a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme.
Abstract: The response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages.
567 citations
University of Cologne1, University of Genoa2, Post Graduate Institute of Medical Education and Research3, Westmead Hospital4, University of Sydney5, Federal University of São Paulo6, Medical University of Graz7, University of California, San Diego8, Innsbruck Medical University9, University of Lagos10, McGill University Health Centre11, Fudan University12, Radboud University Nijmegen13, University of Rennes14, Duke University15, University of Texas Health Science Center at San Antonio16, University of Texas at Austin17, Federal University of Paraná18, University of Texas Health Science Center at Houston19, Cardiff University20, Center for Infectious Disease Research and Policy21
TL;DR: It is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty, and recommended first-line therapy is either voriconazole or isavuconazole, while azole resistance is a concern.
Abstract: Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
519 citations
Peter MacCallum Cancer Centre1, St. Vincent's Health System2, Washington University in St. Louis3, Royal Brisbane and Women's Hospital4, Royal Adelaide Hospital5, University of Western Australia6, University of Newcastle7, La Trobe University8, Fiona Stanley Hospital9, Royal North Shore Hospital10, Liverpool Hospital11, University of Sydney12, Monash University13
TL;DR: In this paper, the authors compared Lutetium-177 [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.
418 citations
01 Jun 2021
TL;DR: Hu et al. as discussed by the authors proposed a pre-trained image processing transformer (IPT) model for denoising, super-resolution and deraining tasks, which is trained on corrupted image pairs with multi-heads and multi-tails.
Abstract: As the computing power of modern hardware is increasing strongly, pre-trained deep learning models (e.g., BERT, GPT-3) learned on large-scale datasets have shown their effectiveness over conventional methods. The big progress is mainly contributed to the representation ability of transformer and its variant architectures. In this paper, we study the low-level computer vision task (e.g., denoising, super-resolution and deraining) and develop a new pre-trained model, namely, image processing transformer (IPT). To maximally excavate the capability of transformer, we present to utilize the well-known ImageNet benchmark for generating a large amount of corrupted image pairs. The IPT model is trained on these images with multi-heads and multi-tails. In addition, the contrastive learning is introduced for well adapting to different image processing tasks. The pre-trained model can therefore efficiently employed on desired task after fine-tuning. With only one pre-trained model, IPT outperforms the current state-of-the-art methods on various low-level benchmarks. Code is available at https://github.com/huawei-noah/Pretrained-IPT and https://gitee.com/mindspore/mindspore/tree/master/model_zoo/research/cv/IPT
416 citations
Centre for Mental Health1, Swansea University2, University of Sydney3, University of Manchester4, University College Cork5, Griffith University6, Stellenbosch University7, Sao Paulo State University8, University of Zagreb9, University of Rochester Medical Center10, University of Udine11, National Taiwan University12, Innsbruck Medical University13, Yale University14, Australian National University15, Johns Hopkins University16, Brigham and Women's Hospital17, University of Auckland18, Hobart Corporation19, Columbia University Medical Center20, University of Oxford21, National Institute for Health Research22, Aga Khan University23, Katholieke Universiteit Leuven24, University of Peradeniya25, University of Bristol26, World Health Organization27, Karolinska Institutet28, First Pavlov State Medical University of St. Peterburg29, Medical University of Vienna30, University of Nottingham31, University of Glasgow32, University of Edinburgh33, Shanghai Jiao Tong University34, Columbia University35, University of Ulm36, University of Oslo37, Goethe University Frankfurt38, Saint Petersburg State University39, University of Toronto40, Sunnybrook Health Sciences Centre41, Waseda University42, Rajarata University of Sri Lanka43, Tel Aviv University44, University Hospitals Bristol NHS Foundation Trust45
TL;DR: In this article, the early effect of the COVID-19 pandemic on suicide rates around the world was assessed using real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature.
413 citations
Evgeny Epifanovsky, Andrew T.B. Gilbert1, Andrew T.B. Gilbert2, Xintian Feng3 +235 more•Institutions (54)
TL;DR: The Q-Chem quantum chemistry program package as discussed by the authors provides a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, and methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques.
Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.
Icahn School of Medicine at Mount Sinai1, Pontifical Catholic University of Chile2, VU University Medical Center3, Cedars-Sinai Medical Center4, Vita-Salute San Raffaele University5, University of Sydney6, Mayo Clinic7, Newcastle University8, Freeman Hospital9, National University of Singapore10, Radboud University Nijmegen11, Royal North Shore Hospital12, Macquarie University13, Kolling Institute of Medical Research14, Jagiellonian University Medical College15, University of Washington Medical Center16, University of Antioquia17, Vancouver General Hospital18, University of Cape Town19
TL;DR: In this paper, the authors presented the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.
University of Las Palmas de Gran Canaria1, Kingston General Hospital2, University of Sydney3, Meir Medical Center4, Ben-Gurion University of the Negev5, University of Wollongong6, The Royal Marsden NHS Foundation Trust7, Okayama University8, University of Wisconsin-Madison9, University of California, Davis10, Merck & Co.11, Johns Hopkins University12
TL;DR: The first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC) was reported in this article.
Abstract: PURPOSEWe report the first 5-year follow-up of any first-line phase III immunotherapy trial for non–small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an op...
TL;DR: In this paper, the in situ formation of a dense, stable, and highly Zn2+ -conductive SEI layer (hopeite) in aqueous Zn chemistry is demonstrated, by introducing Zn(H2 PO4 )2 salt into the electrolyte.
Abstract: Rechargeable aqueous Zn-ion batteries promise high capacity, low cost, high safety, and sustainability for large-scale energy storage The Zn metal anode, however, suffers from the dendrite growth and side reactions that are mainly due to the absence of an appropriate solid electrolyte interphase (SEI) layer Herein, the in situ formation of a dense, stable, and highly Zn2+ -conductive SEI layer (hopeite) in aqueous Zn chemistry is demonstrated, by introducing Zn(H2 PO4 )2 salt into the electrolyte The hopeite SEI (≈140 nm thickness) enables uniform and rapid Zn-ion transport kinetics for dendrite-free Zn deposition, and restrains the side reactions via isolating active Zn from the bulk electrolyte Under practical testing conditions with an ultrathin Zn anode (10 µm), a low negative/positive capacity ratio (≈23), and a lean electrolyte (9 µL mAh-1 ), the Zn/V2 O5 full cell retains 944% of its original capacity after 500 cycles This work provides a simple yet practical solution to high-performance aqueous battery technology via building in situ SEI layers
TL;DR: In this article, a single-pass CO2 utilization of 77% was achieved with a conversion efficiency of 50% toward multicarbon products (ethylene, ethanol, and 1-propanol) at a current density of 1.2 amperes per square centimeter and a full cell voltage of 4.2 volts.
Abstract: Carbon dioxide electroreduction (CO2R) is being actively studied as a promising route to convert carbon emissions to valuable chemicals and fuels. However, the fraction of input CO2 that is productively reduced has typically been very low, <2% for multicarbon products; the balance reacts with hydroxide to form carbonate in both alkaline and neutral reactors. Acidic electrolytes would overcome this limitation, but hydrogen evolution has hitherto dominated under those conditions. We report that concentrating potassium cations in the vicinity of electrochemically active sites accelerates CO2 activation to enable efficient CO2R in acid. We achieve CO2R on copper at pH <1 with a single-pass CO2 utilization of 77%, including a conversion efficiency of 50% toward multicarbon products (ethylene, ethanol, and 1-propanol) at a current density of 1.2 amperes per square centimeter and a full-cell voltage of 4.2 volts.
University College of Medical Sciences1, Kyoto University2, Crozer-Keystone Health System3, Alexandria University4, Nagasaki University5, University of Split6, University of Newcastle7, Queen Mary University of London8, University of Perugia9, University College Cork10, Kobe University11, University of Twente12, Vrije Universiteit Brussel13, University of Hong Kong14, Kwame Nkrumah University of Science and Technology15, Ho Chi Minh City Medicine and Pharmacy University16, University of Bern17, University of Helsinki18, RAND Corporation19, University of Sydney20, University of Barcelona21, University of Vienna22, University of British Columbia23, Kerman Medical University24
Garvan Institute of Medical Research1, University of New South Wales2, Royal Institute of Technology3, University of North Carolina at Chapel Hill4, Harvard University5, Institut Gustave Roussy6, French Institute of Health and Medical Research7, St. Vincent's Health System8, Royal Prince Alfred Hospital9, Princess Alexandra Hospital10, University of Queensland11, University of Sydney12, Shanghai Jiao Tong University13, National University of Singapore14, Agency for Science, Technology and Research15, St George's Hospital16
TL;DR: In this paper, a single-cell and spatially resolved transcriptomics analysis of human breast cancers is presented, which reveals recurrent neoplastic cell heterogeneity and heterotypic interactions play central roles in disease progression.
Abstract: Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed 'ecotypes', with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.
DOI•
15 Nov 2021TL;DR: In this paper, the authors explored whether in-vitro neutralization titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants and used the model to predict the impact of booster vaccination on protection against SARS CoV2 variants.
Abstract: Summary Background Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants. Methods In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. Findings The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (rS=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. Interpretation In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. Funding The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.
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, Berkeley28, University of California, San Francisco29, 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.
TL;DR: The combination of anti-CTLA4 and anti-PD-1 checkpoint inhibitors has been shown to have high activity in melanoma brain metastases as discussed by the authors, but its effect on overall survival is unknown.
Yale University1, University of Sydney2, Emory University3, Aarhus University4, University of Pennsylvania5, Harvard University6, Stanford University7, University of Toronto8, Northwestern University9, St. Joseph's Hospital and Medical Center10, Henry Ford Health System11, University of Florida12, Thomas Jefferson University13, Columbia University14, Duke University15, Icahn School of Medicine at Mount Sinai16, Mayo Clinic17, Johns Hopkins University18, University of California, Los Angeles19, University of Twente20, University of Basel21, Université libre de Bruxelles22
TL;DR: In the early 2000s, a subcommittee of the American Clinical Neurophysiology Society (ACNS) set out to standardize terminology of periodic and rhythmic EEG patterns in the critically ill to aid in future research involving such patterns as mentioned in this paper.
Abstract: In the early 2000s, a subcommittee of the American Clinical Neurophysiology Society (ACNS) set out to “standardize terminology of periodic and rhythmic EEG patterns in the critically ill to aid in future research involving such patterns.” The initial proposed terminology was published in 2005.1 This was presented at many meetings on several continents, subjected to multiple rounds of testing of interrater reliability, underwent many revisions, and was then published as an ACNS guideline in 2013.2 Interrater agreement of the 2012 version (published in early 2013) was very good, with almost perfect agreement for seizures, main terms 1 and 2, the +S modifier, sharpness, absolute amplitude, frequency, and number of phases.3 Agreement was substantial for the +F and +R modifiers (66% and 67%) but was only moderate for triphasic morphology (58%) and fair for evolution (21%, likely at least partly because of the short EEG samples provided).3 The authors concluded that interrater agreement for most terms in the ACNS critical care EEG terminology was high and that these terms were suitable for multicenter research on the clinical significance of these critical care EEG patterns.
With the help of infrastructure funding from the American Epilepsy Society and administrative and website support from the ACNS, a database that incorporated the ACNS terminology was developed for clinical and research purposes, tested during routine clinical care in multiple centers,4 and made available at no cost on the ACNS website (https://www.acns.org/research/critical-care-eeg-monitoring-research-consortium-ccemrc/ccemrc-public-database). This greatly enhanced the ability to complete multicenter investigations.
After the establishment of the standardized terminology and free access to a database incorporating these terms, there have been many investigations into the clinical significance of rhythmic and periodic patterns (RPPs) in critically ill patients. Patterns such as lateralized rhythmic delta activity (LRDA) were found to be highly associated with acute seizures,5,6 equivalent to the association found with lateralized periodic discharges (LPDs) in one study.5 The association of all the main patterns in the nomenclature with seizures was defined in a multicenter cohort of almost 5,000 patients, with seizure rates highest for LPDs, intermediate for LRDA and generalized periodic discharges (GPDs), and lowest for generalized rhythmic delta activity (GRDA).6 This and other studies have shown that several of the modifiers within the nomenclature do indeed have clinically relevant meaning. For example, studies have shown that higher frequency (especially >1.5 Hz), higher prevalence, longer duration, and having a “plus” modifier are all associated with a higher chance of acute seizures.6,7 On the other hand, whether a pattern was spontaneous or “stimulus-induced” did not seem to have a significant effect on its association with seizures.6 In other investigations, the “triphasic morphology” modifier was investigated blindly with multiple expert reviewers, calling into question its relationship with metabolic encephalopathy and its lack of a relationship with seizures.8,9 For patients with refractory status epilepticus treated with anesthetic-induced coma, the presence of “highly epileptiform” bursts suggested that an attempted wean off of anesthetics at that time was much more likely to lead to seizure recurrence than if the bursts were not highly epileptiform.10 Even long-term outcome seemed to be associated with some modifiers, with a higher risk of later epilepsy found if LPDs were more prevalent, had longer duration, or had a “plus” modifier.7
TL;DR: In this paper, the authors used a global database of pesticide applications and a spatially explicit environmental model to estimate the world geography of environmental pollution risk caused by 92 active ingredients in 168 countries.
Abstract: Pesticides are widely used to protect food production and meet global food demand but are also ubiquitous environmental pollutants, causing adverse effects on water quality, biodiversity and human health Here we use a global database of pesticide applications and a spatially explicit environmental model to estimate the world geography of environmental pollution risk caused by 92 active ingredients in 168 countries We considered a region to be at risk of pollution if pesticide residues in the environment exceeded the no-effect concentrations, and to be at high risk if residues exceeded this by three orders of magnitude We find that 64% of global agricultural land (approximately 245 million km2) is at risk of pesticide pollution by more than one active ingredient, and 31% is at high risk Among the high-risk areas, about 34% are in high-biodiversity regions, 5% in water-scarce areas and 19% in low- and lower-middle-income nations We identify watersheds in South Africa, China, India, Australia and Argentina as high-concern regions because they have high pesticide pollution risk, bear high biodiversity and suffer from water scarcity Our study expands earlier pesticide risk assessments as it accounts for multiple active ingredients and integrates risks in different environmental compartments at a global scale Pesticide pollution is a risk for two-thirds of agriculture land A third of high-risk areas are in high-biodiversity regions and a fifth are in low- and lower-middle-income areas, according to environmental modelling combined with pesticide application data
TL;DR: In this paper, the authors show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19.
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
VU University Amsterdam1, University of Bern2, Harvard University3, 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, James I University15, Carlos III Health Institute16, Ohio State University17, Northwestern University18, University of Erlangen-Nuremberg19, University Hospitals Bristol NHS Foundation Trust20, University of Bristol21, 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, The Ohio State University Wexner Medical Center37, Hofstra University38, 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.
University of Sydney1, University of Utah2, Vaccine and Infectious Disease Organization3, University of Glasgow4, University of California, Berkeley5, University of California, San Diego6, University of California, Davis7, Imperial College London8, Pennsylvania State University9, University of Melbourne10, Wellcome Trust11, University of Otago12, Xi'an Jiaotong-Liverpool University13, Texas A&M University14, King's College London15, Medical University of Vienna16, University of Pennsylvania17, University of Arizona18, Scripps Research Institute19, Tulane University20, University of Edinburgh21
TL;DR: In this article, a review of the current scientific evidence that may help clarify the origin of SARS-CoV-2 is presented, with a focus on how severe acute respiratory syndrome coronavirus 2 emerged in the human population.
University of Otago1, Monash University2, University of Kansas3, McMaster University4, University of Oslo5, Sichuan University6, University of Dundee7, University of Sydney8, University of Bari9, Princess Alexandra Hospital10, University of Calgary11, The George Institute for Global Health12, Hôpital Maisonneuve-Rosemont13, University of Alberta14, Royal Adelaide Hospital15, Garvan Institute of Medical Research16, University of Melbourne17, Universidad Autónoma de Nuevo León18, Jiangxi University of Traditional Chinese Medicine19, Cochrane Collaboration20, Population Health Research Institute21
TL;DR: In this paper, the authors evaluated the effect of SGLT-2 inhibitors and GLP-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.
Abstract: Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.
TL;DR: The aim of this work is to design an appropriate SMC law based on an adaptive event-triggered communication scheme such that the resulting closed-loop system could realize stochastic stability and reduce communication burden.
Abstract: In this article, the sliding mode control (SMC) design is studied for a class of stochastic switching systems subject to semi-Markov process via an adaptive event-triggered mechanism. Network-induced communication constraints, semi-Markov switching parameters, and uncertain parameters are considered in a unified framework for the SMC design. Due to the constraint of measuring transducers, the system states always appear with unmeasurable characteristic. Compared with the traditional event-triggered mechanism, the adaptive event-triggered mechanism can effectively reduce the number of triggering than the static event-triggered mechanism. During the data transmission of network communication systems, network-induced delays are characterized from the event trigger to the zero-order holder. The aim of this work is to design an appropriate SMC law based on an adaptive event-triggered communication scheme such that the resulting closed-loop system could realize stochastic stability and reduce communication burden. By introducing the stochastic semi-Markov Lyapunov functional, sojourn-time-dependent sufficient conditions are established for stochastic stability. Then, a suitable SMC law is designed such that the system state can be driven onto the specified sliding surface in a finite-time region. Finally, the simulation study on boost converter circuit model (BCCM) illustrates the effectiveness of the theoretical findings.
Australian National University1, Max Planck Society2, University of Sydney3, University of Ljubljana4, Uppsala University5, Stockholm University6, University of New South Wales7, Monash University8, Macquarie University9, Aarhus University10, Leibniz Institute for Astrophysics Potsdam11, University of Southern Queensland12, International Space Science Institute13, Lund University14, University of Western Australia15, Kapteyn Astronomical Institute16, University of Hertfordshire17, Swinburne University of Technology18, Johns Hopkins University19, York University20, Columbia University21
TL;DR: In this paper, the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
Abstract: © 2021 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
TL;DR: In this article, the authors examined the relationship between international tourism and COVID-19 cases and associated deaths in more than 90 nations and found that a 1% higher level of inbound and outbound tourism is associated with 1.2% and 1.4% higher levels of confirmed cases and death, respectively, controlling for other factors.
Abstract: This study examines the relationship between international tourism and COVID-19 cases and associated deaths in more than 90 nations. We use a cross-country regression analysis and find a positive correlation between international tourism and the cumulated level of COVID-19 confirmed cases and death by April 30, 2020. Our regression analyses show that countries exposed to high flows of international tourism are more prone to cases and deaths caused by the COVID-19 outbreak. This association is robust even after controlling for other socioeconomic determinants of COVID-19 outbreak and regional dummies. Based on our estimations, a 1% higher level of inbound and outbound tourism is associated with 1.2% and 1.4% higher levels of confirmed COVID-19 cases and death, respectively, controlling for other factors. When we normalize the number of cases and death by size of population, the statistical significance remains robust, especially for the COVID-19 deaths, while the effect size reduces.
Oak Ridge National Laboratory1, University of New South Wales2, Ludwig Maximilian University of Munich3, University of Arizona4, Stanford University5, Scripps Institution of Oceanography6, Smithsonian Environmental Research Center7, University of Sydney8, Max Planck Society9, Smithsonian Tropical Research Institute10, Smithsonian Conservation Biology Institute11, Seconda Università degli Studi di Napoli12, University of Leeds13, Aix-Marseille University14, Swiss Federal Institute for Forest, Snow and Landscape Research15, University of California, Santa Barbara16, Commonwealth Scientific and Industrial Research Organisation17, Université Paris-Saclay18, Australian National University19, ETH Zurich20, National University of Singapore21, California Institute of Technology22, Imperial College London23, Northern Arizona University24, Oeschger Centre for Climate Change Research25, Lawrence Berkeley National Laboratory26, University of California, Berkeley27, University of Basel28, Auckland University of Technology29, Indiana University30, University of Oxford31, Spanish National Research Council32, Umeå University33, University of Exeter34, Lawrence Livermore National Laboratory35, University of California, Irvine36, United States Geological Survey37, State University of New York College of Environmental Science and Forestry38, Rutgers University39, Wageningen University and Research Centre40
TL;DR: A range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
Abstract: Atmospheric carbon dioxide concentration ([CO2 ]) is increasing, which increases leaf-scale photosynthesis and intrinsic water-use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2 ] increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2 ]-driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO2 ] (iCO2 ) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre-industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2 , albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.