Showing papers by "Queen's University Belfast published in 2020"
TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.
7,493 citations
University of Coimbra1, University of Southern Queensland2, National Institute for Health and Welfare3, Arizona State University4, Ghent University5, Institute of Technology, Tralee6, University of Ottawa7, Glasgow Caledonian University8, Oregon Health & Science University9, Cambridge University Hospitals NHS Foundation Trust10, George Washington University11, Norwegian Institute of Public Health12, Norwegian School of Sport Sciences13, University of Sydney14, Alberta Health Services15, Queen's University Belfast16, University of Bristol17, Pennington Biomedical Research Center18, University of Cape Town19, University of Regensburg20, University of East Anglia21, University of Granada22, University of Colombo23, National Institutes of Health24, World Health Organization25
TL;DR: New WHO 2020 guidelines on physical activity and sedentary behaviour reaffirm messages that some physical activity is better than none, that more physical Activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours.
Abstract: Objectives To describe new WHO 2020 guidelines on physical activity and sedentary behaviour. Methods The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations. Results The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150-300 min of moderate-intensity, or 75-150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold. Conclusion These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the WHO Global Action Plan on Physical Activity 2018-2030 and to strengthen surveillance systems that track progress towards national and global targets.
3,218 citations
Queen's University Belfast1, University of St Andrews2, Aix-Marseille University3, Historic England4, University of Sheffield5, University of Oxford6, Alfred Wegener Institute for Polar and Marine Research7, Xi'an Jiaotong University8, University of Minnesota9, Nanjing Normal University10, University of Hohenheim11, University of Kiel12, University of California, Santa Cruz13, Lawrence Livermore National Laboratory14, ETH Zurich15, University of Waikato16, Woods Hole Oceanographic Institution17, Heidelberg University18, Cornell University19, Lund University20, University of New South Wales21, University of Arizona22, University of Groningen23, University of Bristol24, University of Glasgow25, University of California, Irvine26, University of Bern27, Aarhus University28, Nagoya University29, Swiss Federal Institute for Forest, Snow and Landscape Research30, National Museum of Japanese History31, University of Bologna32
TL;DR: In this article, the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP.
Abstract: Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
2,800 citations
Donostia International Physics Center1, Rovira i Virgili University2, MacDiarmid Institute for Advanced Materials and Nanotechnology3, Victoria University of Wellington4, University of Cambridge5, University of California, Santa Barbara6, Queen's University Belfast7, Technical University of Denmark8, University of Victoria9, Chung-Ang University10, University of Jena11, Leibniz Institute of Photonic Technology12, Rutgers University13, University of Strathclyde14, University of Liverpool15, University of Iowa16, University of Minnesota17, Heidelberg University18, National Institute of Advanced Industrial Science and Technology19, Chalmers University of Technology20, Humboldt University of Berlin21, University of Michigan22, Jiangnan University23, Stanford University24, Xiamen University25, Ludwig Maximilian University of Munich26, Hokkaido University27, Seoul National University28, University of Illinois at Urbana–Champaign29, Kwansei Gakuin University30, University of Vigo31, Free University of Berlin32, Northwestern University33, University of Duisburg-Essen34, National Research Council35, Indian Institute of Science Education and Research, Thiruvananthapuram36, Duke University37, Northeastern University (China)38, Temple University39, Wuhan University40, Japan Advanced Institute of Science and Technology41, Jilin University42, Ikerbasque43
TL;DR: Prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.
Abstract: The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.
1,768 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
University of Ottawa1, World Health Organization2, University of Pittsburgh3, King Saud bin Abdulaziz University for Health Sciences4, University of Edinburgh5, University of Jena6, Utrecht University7, Oswaldo Cruz Foundation8, Monash University9, Public Health England10, University of Liverpool11, Liverpool School of Tropical Medicine12, University of Oxford13, The Chinese University of Hong Kong14, Imperial College London15, Sungkyunkwan University16, Trinity College, Dublin17, Queen's University Belfast18, Johns Hopkins University19, Radboud University Nijmegen20, University of Bonn21, Seoul National University22, University of Brescia23, Beijing University of Chinese Medicine24, Centers for Disease Control and Prevention25, Tianjin University of Traditional Chinese Medicine26
TL;DR: A minimum set of common outcome measures for studies of COVID-19, which includes a measure of viral burden, patient survival, and patient progression through the health-care system by use of the WHO Clinical Progression Scale are urged.
Abstract: Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
882 citations
University of Sheffield1, Alfred Wegener Institute for Polar and Marine Research2, Aix-Marseille University3, Queen's University Belfast4, University of St Andrews5, University of Oxford6, University of Kiel7, Woods Hole Oceanographic Institution8, Heidelberg University9, Williams College10, Aarhus University11, University of Cambridge12
TL;DR: Marine20 as mentioned in this paper is an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radioccarbon from 0 −55 cal kBP and serves as a baseline for regional oceanic variation.
Abstract: The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.
690 citations
University of Pittsburgh1, Utrecht University2, Imperial College Healthcare3, Université Paris-Saclay4, King Saud bin Abdulaziz University for Health Sciences5, University of Oxford6, St. Michael's Hospital7, University of Bristol8, Monash University9, University of Amsterdam10, NHS Blood and Transplant11, University of Antwerp12, Mahidol University13, Princess Alexandra Hospital14, Université de Sherbrooke15, University Health Network16, University of Western Australia17, University of Toronto18, Queen's University Belfast19, Health Research Council of New Zealand20, Auckland City Hospital21, University of British Columbia22, University of Auckland23, Radboud University Nijmegen24, The George Institute for Global Health25, University of Manitoba26, University of California, Los Angeles27, UCLA Medical Center28, St John of God Subiaco Hospital29
TL;DR: To determine whether hydrocortisone improves outcome for patients with severe COVID-19, an ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin was conducted.
Abstract: Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration ClinicalTrials.gov Identifier:NCT02735707
630 citations
TL;DR: Current mycotoxin occurrenceabove the EU and Codex limits appears to confirm the FAO 25% estimate, while this figure greatly underestimates the occurrence above the detectable levels (up to 60–80%).
Abstract: Prior to 1985 the Food and Agriculture Organization (FAO) estimated global food crop contamination with mycotoxins to be 25%. The origin of this statement is largely unknown. To assess the rationale for it, the relevant literature was reviewed and data of around 500,000 analyses from the European Food Safety Authority and large global survey for aflatoxins, fumonisins, deoxynivalenol, T-2 and HT-2 toxins, zearalenone and ochratoxin A in cereals and nuts were examined. Using different thresholds, i.e. limit of detection, the lower and upper regulatory limits of European Union (EU) legislation and Codex Alimentarius standards, the mycotoxin occurrence was estimated. Impact of different aspects on uncertainty of the occurrence estimates presented in literature and related to our results are critically discussed. Current mycotoxin occurrence above the EU and Codex limits appears to confirm the FAO 25% estimate, while this figure greatly underestimates the occurrence above the detectable levels (up to 60-80%). The high occurrence is likely explained by a combination of the improved sensitivity of analytical methods and impact of climate change. It is of immense importance that the detectable levels are not overlooked as through diets, humans are exposed to mycotoxin mixtures which can induce combined adverse health effects.
563 citations
University of Waikato1, University of New South Wales2, University of Sheffield3, Australian Nuclear Science and Technology Organisation4, University of California, Irvine5, Historic England6, University of Auckland7, University of Oxford8, University of Arizona9, James Cook University10, Queen's University Belfast11, ETH Zurich12
TL;DR: In this article, the Southern Hemisphere curve (SHCal20) is proposed to estimate the mean Southern Hemisphere offset to be 36 ± 27 14C yrs older than the Northern Hemisphere offset, based upon a comparison of Southern Hemisphere tree-ring data compared with contemporaneous Northern Hemisphere data.
Abstract: Early researchers of radiocarbon levels in Southern Hemisphere tree rings identified a variable North-South hemispheric offset, necessitating construction of a separate radiocarbon calibration curve for the South. We present here SHCal20, a revised calibration curve from 0–55,000 cal BP, based upon SHCal13 and fortified by the addition of 14 new tree-ring data sets in the 2140–0, 3520–3453, 3608–3590 and 13,140–11,375 cal BP time intervals. We detail the statistical approaches used for curve construction and present recommendations for the use of the Northern Hemisphere curve (IntCal20), the Southern Hemisphere curve (SHCal20) and suggest where application of an equal mixture of the curves might be more appropriate. Using our Bayesian spline with errors-in-variables methodology, and based upon a comparison of Southern Hemisphere tree-ring data compared with contemporaneous Northern Hemisphere data, we estimate the mean Southern Hemisphere offset to be 36 ± 27 14C yrs older.
535 citations
TL;DR: Supportive interventions to reduce loneliness should prioritise younger people and those with mental health symptoms, and improving emotion regulation and sleep quality, and increasing social support may be optimal initial targets to reduce the impact of COVID-19 regulations on mental health outcomes.
Abstract: Objectives Loneliness is a significant public health issue. The COVID-19 pandemic has resulted in lockdown measures limiting social contact. The UK public are worried about the impact of these measures on mental health outcomes. Understanding the prevalence and predictors of loneliness at this time is a priority issue for research. Method The study employed a cross-sectional online survey design. Baseline data collected between March 23rd and April 24th 2020 from UK adults in the COVID-19 Psychological Wellbeing Study were analysed (N = 1964, 18-87 years, M = 37.11, SD = 12.86, 70% female). Logistic regression analysis examined the influence of sociodemographic, social, health and COVID-19 specific factors on loneliness. Results The prevalence of loneliness was 27% (530/1964). Risk factors for loneliness were younger age group (OR: 4.67-5.31), being separated or divorced (OR: 2.29), scores meeting clinical criteria for depression (OR: 1.74), greater emotion regulation difficulties (OR: 1.04), and poor quality sleep due to the COVID-19 crisis (OR: 1.30). Higher levels of social support (OR: 0.92), being married/co-habiting (OR: 0.35) and living with a greater number of adults (OR: 0.87) were protective factors. Conclusions Rates of loneliness during the initial phase of lockdown were high. Risk factors were not specific to the COVID-19 crisis. Findings suggest that supportive interventions to reduce loneliness should prioritise younger people and those with mental health symptoms. Improving emotion regulation and sleep quality, and increasing social support may be optimal initial targets to reduce the impact of COVID-19 regulations on mental health outcomes.
University of Nottingham1, University of London2, University of Edinburgh3, University College London4, University of Oxford5, University of Leicester6, University of Cambridge7, NHS England8, Swansea University9, Queen Mary University of London10, University of Liverpool11, Queen's University Belfast12
TL;DR: The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19, and has the potential to be dynamically updated as the pandemic evolves.
Abstract: OBJECTIVE: To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults. DESIGN: Population based cohort study. SETTING AND PARTICIPANTS: QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020. MAIN OUTCOME MEASURES: The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period. RESULTS: 4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R2); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19. CONCLUSION: The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.
TL;DR: In this article, the authors survey three new multiple antenna technologies that can play key roles in beyond 5G networks: cell-free massive MIMO, beamspace massive mIMO and intelligent reflecting surfaces.
Abstract: Multiple antenna technologies have attracted much research interest for several decades and have gradually made their way into mainstream communication systems. Two main benefits are adaptive beamforming gains and spatial multiplexing, leading to high data rates per user and per cell, especially when large antenna arrays are adopted. Since multiple antenna technology has become a key component of the fifth-generation (5G) networks, it is time for the research community to look for new multiple antenna technologies to meet the immensely higher data rate, reliability, and traffic demands in the beyond 5G era. Radically new approaches are required to achieve orders-of-magnitude improvements in these metrics. There will be large technical challenges, many of which are yet to be identified. In this paper, we survey three new multiple antenna technologies that can play key roles in beyond 5G networks: cell-free massive MIMO, beamspace massive MIMO, and intelligent reflecting surfaces. For each of these technologies, we present the fundamental motivation, key characteristics, recent technical progresses, and provide our perspectives for future research directions. The paper is not meant to be a survey/tutorial of a mature subject, but rather serve as a catalyst to encourage more research and experiments in these multiple antenna technologies.
QIMR Berghofer Medical Research Institute1, Charité2, University of Alabama at Birmingham3, Charles University in Prague4, National Institutes of Health5, Paris Descartes University6, St. Michael's Hospital7, Istituto Giannina Gaslini8, University of Auckland9, Nanyang Technological University10, Cystic Fibrosis Trust11, European Medicines Agency12, University of Washington13, University of Wisconsin-Madison14, University of British Columbia15, Katholieke Universiteit Leuven16, Seattle Children's Research Institute17, Post Graduate Institute of Medical Education and Research18, University College Dublin19, University of Giessen20, University of Michigan21, Queen's University Belfast22, Johns Hopkins University23, University of Liverpool24, Woolcock Institute of Medical Research25, University of Toronto26, University of Cape Town27
TL;DR: Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet.
TL;DR: In this paper, the main strategies for climate change abatement, namely conventional mitigation, negative emissions and radiative forcing geoengineering, are reviewed, and it is evident that conventional mitigation efforts alone are not sufficient to meet the targets stipulated by the Paris agreement; therefore, the utilization of alternative routes appears inevitable.
Abstract: Climate change is defined as the shift in climate patterns mainly caused by greenhouse gas emissions from natural systems and human activities. So far, anthropogenic activities have caused about 1.0 °C of global warming above the pre-industrial level and this is likely to reach 1.5 °C between 2030 and 2052 if the current emission rates persist. In 2018, the world encountered 315 cases of natural disasters which are mainly related to the climate. Approximately 68.5 million people were affected, and economic losses amounted to $131.7 billion, of which storms, floods, wildfires and droughts accounted for approximately 93%. Economic losses attributed to wildfires in 2018 alone are almost equal to the collective losses from wildfires incurred over the past decade, which is quite alarming. Furthermore, food, water, health, ecosystem, human habitat and infrastructure have been identified as the most vulnerable sectors under climate attack. In 2015, the Paris agreement was introduced with the main objective of limiting global temperature increase to 2 °C by 2100 and pursuing efforts to limit the increase to 1.5 °C. This article reviews the main strategies for climate change abatement, namely conventional mitigation, negative emissions and radiative forcing geoengineering. Conventional mitigation technologies focus on reducing fossil-based CO2 emissions. Negative emissions technologies are aiming to capture and sequester atmospheric carbon to reduce carbon dioxide levels. Finally, geoengineering techniques of radiative forcing alter the earth’s radiative energy budget to stabilize or reduce global temperatures. It is evident that conventional mitigation efforts alone are not sufficient to meet the targets stipulated by the Paris agreement; therefore, the utilization of alternative routes appears inevitable. While various technologies presented may still be at an early stage of development, biogenic-based sequestration techniques are to a certain extent mature and can be deployed immediately.
The Royal Marsden NHS Foundation Trust1, Institute of Cancer Research2, University College London Hospitals NHS Foundation Trust3, Beatson West of Scotland Cancer Centre4, Clatterbridge Cancer Centre NHS Foundation Trust5, University of Leeds6, Queen's University Belfast7, Musgrove Park Hospital8, Blackburn College9, University of Southampton10, Royal Sussex County Hospital11, Western General Hospital12, Royal Lancaster Infirmary13, Cardiff University14
TL;DR: The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer by recruiting participants from 17 UK hospitals and following follow-up for a period of 24·8 months.
Abstract: Summary Background Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer. Methods In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-the-winner) design, we recruited participants from 17 UK hospitals. Men aged 18 years or older with progressing metastatic castration-resistant prostate cancer previously treated with one or two taxane chemotherapy regimens and with an Eastern Cooperative Oncology Group performance status of 2 or less had tumour biopsies tested with targeted sequencing. Patients with DDR gene aberrations were randomly assigned (1:1) by a computer-generated minimisation method, with balancing for circulating tumour cell count at screening, to receive 400 mg or 300 mg olaparib twice daily, given continuously in 4-week cycles until disease progression or unacceptable toxicity. Neither participants nor investigators were masked to dose allocation. The primary endpoint of confirmed response was defined as a composite of all patients presenting with any of the following outcomes: radiological objective response (as assessed by Response Evaluation Criteria in Solid Tumors 1.1), a decrease in prostate-specific antigen (PSA) of 50% or more (PSA50) from baseline, or conversion of circulating tumour cell count (from ≥5 cells per 7·5 mL blood at baseline to ClinicalTrials.gov , NCT01682772 . Recruitment for the trial has completed and follow-up is ongoing. Findings 711 patients consented for targeted screening between April 1, 2015, and Aug 30, 2018. 161 patients had DDR gene aberrations, 98 of whom were randomly assigned and treated (49 patients for each olaparib dose), with 92 evaluable for the primary endpoint (46 patients for each olaparib dose). Median follow-up was 24·8 months (IQR 16·7–35·9). Confirmed composite response was achieved in 25 (54·3%; 95% CI 39·0–69·1) of 46 evaluable patients in the 400 mg cohort, and 18 (39·1%; 25·1–54·6) of 46 evaluable patients in the 300 mg cohort. Radiological response was achieved in eight (24·2%; 11·1–42·3) of 33 evaluable patients in the 400 mg cohort and six (16·2%; 6·2–32·0) of 37 in the 300 mg cohort; PSA50 response was achieved in 17 (37·0%; 23·2–52·5) of 46 and 13 (30·2%; 17·2–46·1) of 43; and circulating tumour cell count conversion was achieved in 15 (53·6%; 33·9–72·5) of 28 and 13 (48·1%; 28·7–68·1) of 27. The most common grade 3–4 adverse event in both cohorts was anaemia (15 [31%] of 49 patients in the 300 mg cohort and 18 [37%] of 49 in the 400 mg cohort). 19 serious adverse reactions were reported in 13 patients. One death possibly related to treatment (myocardial infarction) occurred after 11 days of treatment in the 300 mg cohort. Interpretation Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations, supporting the implementation of genomic stratification of metastatic castration-resistant prostate cancer in clinical practice. Funding Cancer Research UK, AstraZeneca, Prostate Cancer UK, the Prostate Cancer Foundation, the Experimental Cancer Medicine Centres Network, and the National Institute for Health Research Biomedical Research Centres.
TL;DR: The findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.
Abstract: Objective Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. Design We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). Results Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. Conclusion Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.
Tsinghua University1, Beijing University of Technology2, East China University of Science and Technology3, University of Science and Technology of China4, Chinese Academy of Sciences5, Beijing University of Chemical Technology6, Sun Yat-sen University7, Queen's University Belfast8, Tianjin University of Technology9, University of California, Los Angeles10
TL;DR: A general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.
Abstract: Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a promising family of materials to investigate. Herein we developed a general host–guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M1/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir1/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$ whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10−3 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$). The activity of Ir1/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir1/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir1/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst. Single-atom catalysts maximize metal atom efficiency and exhibit properties that can be considerably different to their nanoparticle equivalent. Now a general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.
Hull York Medical School1, Sahlgrenska University Hospital2, Lithuanian University of Health Sciences3, University of Cambridge4, King's College London5, Albert Einstein College of Medicine6, Autonomous University of Barcelona7, University of Glasgow8, Guangzhou Medical University9, Queen's University Belfast10, Cochrane Collaboration11, McMaster University12, University of Manchester13, University of Ulsan14, University of Bern15, Erasmus University Medical Center16, University of Vienna17
TL;DR: In adults, cough hypersensitivity has become the overarching diagnosis, and in children, persistent bacterial bronchitis explains most wet cough, changing treatment advice.
Abstract: These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.
Duke University1, University of California, Los Angeles2, Tufts University3, Queen's University Belfast4, University of Miami5, University of Bonn6, University of Paris7, Vita-Salute San Raffaele University8, Tokyo Medical and Dental University9, University of Wisconsin-Madison10, Peking University11, University of Pennsylvania12, Case Western Reserve University13, University College London14, Emory University15, Oregon Health & Science University16, University of Melbourne17, National Institutes of Health18, Massachusetts Institute of Technology19
TL;DR: The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.
TL;DR: The impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2, is examined.
Abstract: Summary Background During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2. Methods In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008–17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013–16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I–III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1–6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred. Findings Across England in 2013–16, an average of 6281 patients with stage I–III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1–3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3–8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type. Interpretation Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer. Funding None.
TL;DR: There is no one-size-fits-all approach to addressing loneliness or social isolation, and hence the need to tailor interventions to suit the needs of individuals, specific groups or the degree of loneliness experienced.
Abstract: Loneliness and social isolation are growing public health concerns in our ageing society. Whilst these experiences occur across the life span, 50% of individuals aged over 60 are at risk of social isolation and one-third will experience some degree of loneliness later in life. The aim of this scoping review was to describe the range of interventions to reduce loneliness and social isolation among older adults that have been evaluated; in terms of intervention conceptualisation, categorisation, and components. Three electronic databases (CINAHL, Embase and Medline) were systematically searched for relevant published reviews of interventions for loneliness and social isolation. Inclusion criteria were: review of any type, published in English, a target population of older people and reported data on the categorisation of loneliness and/or social isolation interventions. Data extracted included: categories of interventions and the reasoning underpinning this categorisation. The methodology framework proposed by Arskey and O’Malley and further developed by Levac, et al. was used to guide the scoping review process. A total of 33 reviews met the inclusion criteria, evaluating a range of interventions targeted at older people residing in the community or institutionalised settings. Authors of reviews included in this paper often used the same terms to categorise different intervention components and many did not provide a clear definition of these terms. There were inconsistent meanings attributed to intervention characteristics. Overall, interventions were commonly categorised on the basis of: 1) group or one-to-one delivery mode, 2) the goal of the intervention, and 3) the intervention type. Several authors replicated the categorisation system used in previous reviews. Many interventions have been developed to combat loneliness and social isolation among older people. The individuality of the experience of loneliness and isolation may cause difficulty in the delivery of standardised interventions. There is no one-size-fits-all approach to addressing loneliness or social isolation, and hence the need to tailor interventions to suit the needs of individuals, specific groups or the degree of loneliness experienced. Therefore, future research should be aimed at discerning what intervention works for whom, in what particular context and how.
TL;DR: The virological characteristics of SARS-CoV-2 and clinical course of COVID-19 are described with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options.
TL;DR: This work uses the correlation of molecular weight and ion mobility in a trapped ion mobility device to devise a scan mode that samples up to 100% of the peptide precursor ion current in m/z and mobility windows and thereby increase the specificity for precursor identification.
Abstract: Data-independent acquisition modes isolate and concurrently fragment populations of different precursors by cycling through segments of a predefined precursor m/z range. Although these selection windows collectively cover the entire m/z range, overall, only a few per cent of all incoming ions are isolated for mass analysis. Here, we make use of the correlation of molecular weight and ion mobility in a trapped ion mobility device (timsTOF Pro) to devise a scan mode that samples up to 100% of the peptide precursor ion current in m/z and mobility windows. We extend an established targeted data extraction workflow by inclusion of the ion mobility dimension for both signal extraction and scoring and thereby increase the specificity for precursor identification. Data acquired from whole proteome digests and mixed organism samples demonstrate deep proteome coverage and a high degree of reproducibility as well as quantitative accuracy, even from 10 ng sample amounts. diaPASEF makes use of the correlation between the ion mobility and the m/z of peptides to trap and release precursor ions in a TIMS-TOF mass spectrometer for an almost complete sampling of the precursor ion beam with data-independent acquisition.
Harvard University1, University of Washington2, Humboldt University of Berlin3, Imperial College London4, University of Belgrade5, Istituto Nazionale di Fisica Nucleare6, Technical University of Berlin7, University of Bordeaux8, University of Oxford9, University of Valencia10, University of Strathclyde11, Rutherford Appleton Laboratory12, King's College London13, Foundation for Research & Technology – Hellas14, University of Birmingham15, University College London16, University of Liverpool17, National Physical Laboratory18, University of Nottingham19, University of Sussex20, Fermilab21, Northern Illinois University22, Peking University23, University of Pisa24, University of California, Riverside25, University of Nevada, Reno26, CERN27, University of Niš28, National Institute of Chemical Physics and Biophysics29, Beni-Suef University30, British University in Egypt31, Leibniz University of Hanover32, Paul Sabatier University33, University of Paris34, University of Cambridge35, Wayne State University36, Stanford University37, University of Bergen38, University of Amsterdam39, Northwestern University40, University of Bristol41, University of Warsaw42, University of Illinois at Urbana–Champaign43, Fayoum University44, University of Crete45, Queen's University Belfast46, Brandeis University47, University of Bologna48, Cochin University of Science and Technology49, German Aerospace Center50, University of Manchester51, University of Copenhagen52, University of Düsseldorf53, University of Vienna54, Florida State University55, University of Florence56, University of Illinois at Chicago57, University of Bremen58, University of Mainz59, Chinese Academy of Sciences60, University of Cincinnati61
TL;DR: The Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE) as mentioned in this paper is a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments.
Abstract: We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity.
TL;DR: An international team of scientists with long‐standing expertise in SERS is presented by presenting considerations on reliable and quantitative SERS to increase the inter‐laboratory comparability of experimental SERS results and further establish SERS as an analytical tool.
Abstract: Experimental results obtained in different laboratories world-wide by researchers using surface-enhanced Raman scattering (SERS) can differ significantly. We, an international team of scientists with long-standing expertise in SERS, address this issue from our perspective by presenting considerations on reliable and quantitative SERS. The central idea of this joint effort is to highlight key parameters and pitfalls that are often encountered in the literature. To that end, we provide here a series of recommendations on: a) the characterization of solid and colloidal SERS substrates by correlative electron and optical microscopy and spectroscopy, b) on the determination of the SERS enhancement factor (EF), including suitable Raman reporter/probe molecules, and finally on c) good analytical practice. We hope that both newcomers and specialists will benefit from these recommendations to increase the inter-laboratory comparability of experimental SERS results and further establish SERS as an analytical tool.
University College London1, Oregon Health & Science University2, Harvard University3, Lund University4, Vita-Salute San Raffaele University5, University of Manchester6, University of British Columbia7, Monash University8, The Royal Marsden NHS Foundation Trust9, Columbia University10, University of Texas MD Anderson Cancer Center11, University of California, Davis12, University of Bologna13, University of California, San Francisco14, Institut Gustave Roussy15, Duke University16, University of Cologne17, Medical University of Vienna18, University of Oslo19, University of Washington20, Fred Hutchinson Cancer Research Center21, Peter MacCallum Cancer Centre22, University of Melbourne23, Northwestern University24, Cornell University25, Memorial Sloan Kettering Cancer Center26, American University of Beirut27, Tel Aviv University28, National and Kapodistrian University of Athens29, Tata Memorial Hospital30, Icahn School of Medicine at Mount Sinai31, Ghent University32, Belfast City Hospital33, Queen's University Belfast34, The Chinese University of Hong Kong35, University of California, Los Angeles36, University of Bern37, University of Minnesota38, Université de Montréal39, Tulane University40, Prostate Cancer Foundation41, University of Hamburg42, Toho University43, Université catholique de Louvain44, Radboud University Nijmegen45, University of St. Gallen46
TL;DR: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse and provide a practical guide to help clinicians discuss therapeutic options with patients.
TL;DR: This guidance document provides a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia and defines two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge.
Abstract: The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.
TL;DR: In this article, a comprehensive overview of the underlying physics relevant to an understanding of materials processing during the various production steps in extrusion-based 3D concrete printing (3DCP) is presented.
TL;DR: New technologies, including scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness.