Showing papers by "University of Western Australia published in 2018"
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
TL;DR: If current trends continue, the 2025 global physical activity target (a 10% relative reduction in insufficient physical activity) will not be met and policies to increase population levels of physical activity need to be prioritised and scaled up urgently.
2,358 citations
TL;DR: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.
Abstract: An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.
2,118 citations
TL;DR: It is found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero.
1,831 citations
TL;DR: This work presents a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and shows that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
1,620 citations
TL;DR: This analysis expands upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars.
Abstract: On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars. Our analysis employs two methods: the use of equation-of-state-insensitive relations between various macroscopic properties of the neutron stars and the use of an efficient parametrization of the defining function pðρÞ of the equation of state itself. From the LIGO and Virgo data alone and the first method, we measure the two neutron star radii as R1 ¼ 10.8 þ2.0 −1.7 km for the heavier star and R2 ¼ 10.7 þ2.1 −1.5 km for the lighter star at the 90% credible level. If we additionally require that the equation of state supports neutron stars with masses larger than 1.97 M⊙ as required from electromagnetic observations and employ the equation-of-state parametrization, we further constrain R1 ¼ 11.9 þ1.4 −1.4 km and R2 ¼ 11.9 þ1.4 −1.4 km at the 90% credible level. Finally, we obtain constraints on pðρÞ at supranuclear densities, with pressure at twice nuclear saturation density measured at 3.5 þ2.7 −1.7 × 1034 dyn cm−2 at the 90% level.
1,595 citations
TL;DR: A comprehensive survey on adversarial attacks on deep learning in computer vision can be found in this paper, where the authors review the works that design adversarial attack, analyze the existence of such attacks and propose defenses against them.
Abstract: Deep learning is at the heart of the current rise of artificial intelligence. In the field of computer vision, it has become the workhorse for applications ranging from self-driving cars to surveillance and security. Whereas, deep neural networks have demonstrated phenomenal success (often beyond human capabilities) in solving complex problems, recent studies show that they are vulnerable to adversarial attacks in the form of subtle perturbations to inputs that lead a model to predict incorrect outputs. For images, such perturbations are often too small to be perceptible, yet they completely fool the deep learning models. Adversarial attacks pose a serious threat to the success of deep learning in practice. This fact has recently led to a large influx of contributions in this direction. This paper presents the first comprehensive survey on adversarial attacks on deep learning in computer vision. We review the works that design adversarial attacks, analyze the existence of such attacks and propose defenses against them. To emphasize that adversarial attacks are possible in practical conditions, we separately review the contributions that evaluate adversarial attacks in the real-world scenarios. Finally, drawing on the reviewed literature, we provide a broader outlook of this research direction.
1,542 citations
University of Rochester1, French Institute of Health and Medical Research2, Institute for Health Metrics and Evaluation3, Cairo University4, University of Extremadura5, Debre Berhan University6, University of Cambridge7, Seoul National University Hospital8, Autonomous University of Chile9, University of Pennsylvania10, Haramaya University11, Humboldt University of Berlin12, Karolinska Institutet13, McGill University14, Imperial College London15, West Virginia University16, University of Western Australia17, Hawassa University18, Tehran University of Medical Sciences19, Jordan University of Science and Technology20, Seoul National University21, Xiamen University22, University of Bari23, University of Porto24, National University of Malaysia25, University of Sydney26, Baqiyatallah University of Medical Sciences27, Iran University of Medical Sciences28, Mekelle University29, University of Western Sydney30, University of Ibadan31, Deakin University32, La Trobe University33, Ahvaz Jundishapur University of Medical Sciences34, University of Maragheh35, Utkal University36, University of North Carolina at Charlotte37, New York University38
TL;DR: Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors.
Abstract: Summary Background Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. Methods Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, 6·1 million (95% uncertainty interval [UI] 5·0–7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0–3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1–25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2–79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6–4·0) DALYs and 211 296 deaths (95% UI 167 771–265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36–1·43) and 1990 (1·37, 1·34–1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index. Interpretation Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially. Funding Bill & Melinda Gates Foundation.
1,388 citations
James Cook University1, National Oceanic and Atmospheric Administration2, Australian Institute of Marine Science3, University of Victoria4, King Abdullah University of Science and Technology5, Queensland Museum6, Lancaster University7, Curtin University8, University of Western Australia9, University of Queensland10
TL;DR: Coral reefs in the present day have less time than in earlier periods to recover from bleaching events, and Tropical reef systems are transitioning to a new era in which the interval between recurrent bouts of coral bleaching is too short for a full recovery of mature assemblages.
Abstract: Tropical reef systems are transitioning to a new era in which the interval between recurrent bouts of coral bleaching is too short for a full recovery of mature assemblages. We analyzed bleaching records at 100 globally distributed reef locations from 1980 to 2016. The median return time between pairs of severe bleaching events has diminished steadily since 1980 and is now only 6 years. As global warming has progressed, tropical sea surface temperatures are warmer now during current La Nina conditions than they were during El Nino events three decades ago. Consequently, as we transition to the Anthropocene, coral bleaching is occurring more frequently in all El Nino–Southern Oscillation phases, increasing the likelihood of annual bleaching in the coming decades.
Université Paris-Saclay1, Netherlands Cancer Institute2, University of Siena3, University of Sydney4, University of Queensland5, Peter MacCallum Cancer Centre6, Alfred Hospital7, The Royal Marsden NHS Foundation Trust8, University of Western Australia9, Curie Institute10, University of Duisburg-Essen11, Radboud University Nijmegen Medical Centre12, Hannover Medical School13, Université de Montréal14, Washington University in St. Louis15, Merck & Co.16
TL;DR: As adjuvant therapy for high‐risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence‐free survival than placebo, with no new toxic effects identified.
Abstract: Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. Results At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence...
Monash University1, National Health and Medical Research Council2, University of New South Wales3, University of Pennsylvania4, Erasmus University Rotterdam5, Oulu University Hospital6, University of Adelaide7, Odense University Hospital8, State University of New York System9, Australian Catholic University10, University Medical Center Utrecht11, Sanjay Gandhi Post Graduate Institute of Medical Sciences12, University of Chile13, university of lille14, Utrecht University15, Imperial College London16, University of Western Australia17, Karolinska Institutet18, University of Rochester19, Pennsylvania State University20, Peking University21, Cornell University22, Royal College of Surgeons in Ireland23, University of Hong Kong24, Columbia University Medical Center25, Pennington Biomedical Research Center26, Agostino Gemelli University Polyclinic27, Deakin University28, Universidade Federal do Rio Grande do Sul29, Victoria University, Australia30, University of Helsinki31, Queen Mary University of London32, Taipei Medical University Hospital33, University of Cape Town34, Norwegian University of Science and Technology35, Children's Hospital of Philadelphia36, University of Colombo37, University of Pittsburgh38, Boston Children's Hospital39, Hacettepe University40
TL;DR: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.
Abstract: Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study Funding/Competing Interest(S) The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
Dalhousie University1, University of Tasmania2, University of New South Wales3, Scottish Association for Marine Science4, Aberystwyth University5, Marine Biological Association of the United Kingdom6, University of Western Australia7, Australian Institute of Marine Science8, Commonwealth Scientific and Industrial Research Organisation9, Pacific Marine Environmental Laboratory10, University of Washington11
TL;DR: Using a range of ocean temperature data including global records of daily satellite observations, daily in situ measurements and gridded monthly in situ-based data sets, this work identifies significant increases in marine heatwaves over the past century.
Abstract: Heatwaves are important climatic extremes in atmospheric and oceanic systems that can have devastating and long-term impacts on ecosystems, with subsequent socioeconomic consequences. Recent prominent marine heatwaves have attracted considerable scientific and public interest. Despite this, a comprehensive assessment of how these ocean temperature extremes have been changing globally is missing. Using a range of ocean temperature data including global records of daily satellite observations, daily in situ measurements and gridded monthly in situ-based data sets, we identify significant increases in marine heatwaves over the past century. We find that from 1925 to 2016, global average marine heatwave frequency and duration increased by 34% and 17%, respectively, resulting in a 54% increase in annual marine heatwave days globally. Importantly, these trends can largely be explained by increases in mean ocean temperatures, suggesting that we can expect further increases in marine heatwave days under continued global warming.
TL;DR: Current treatment strategies for rheumatoid arthritis are reviewed and how such insights could ultimately lead to the earlier diagnosis of RA - as well as providing new opportunities for drug treatment and prevention through behavioral changes in high-risk individuals.
Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.
TL;DR: In this article, the authors present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves.
Abstract: We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.
TL;DR: This work recognizes three waves of mycorrhizal evolution, starting with AM in early land plants, continuing in the Cretaceous with multiple new NM or EcM linages, ericoid and orchid mycor rhizas, which has resulted in root complexity linked to rapid plant diversification in biodiversity hotspots.
Abstract: Contents Summary 1108 I. Introduction 1108 II. Mycorrhizal plant diversity at global and local scales 1108 III. Mycorrhizal evolution in plants: a brief update 1111 IV. Conclusions and perspectives 1114 References 1114 SUMMARY: The majority of vascular plants are mycorrhizal: 72% are arbuscular mycorrhizal (AM), 2.0% are ectomycorrhizal (EcM), 1.5% are ericoid mycorrhizal and 10% are orchid mycorrhizal. Just 8% are completely nonmycorrhizal (NM), whereas 7% have inconsistent NM-AM associations. Most NM and NM-AM plants are nutritional specialists (e.g. carnivores and parasites) or habitat specialists (e.g. hydrophytes and epiphytes). Mycorrhizal associations are consistent in most families, but there are exceptions with complex roots (e.g. both EcM and AM). We recognize three waves of mycorrhizal evolution, starting with AM in early land plants, continuing in the Cretaceous with multiple new NM or EcM linages, ericoid and orchid mycorrhizas. The third wave, which is recent and ongoing, has resulted in root complexity linked to rapid plant diversification in biodiversity hotspots.
Evangelos Evangelou1, Evangelos Evangelou2, Helen R. Warren3, Helen R. Warren4 +338 more•Institutions (93)
TL;DR: In this article, the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry was conducted.
Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future
University of Cambridge1, Australian National University2, Norwegian Institute of Public Health3, Utrecht University4, University of Tromsø5, University of Oxford6, Johns Hopkins University7, The George Institute for Global Health8, National Institutes of Health9, Copenhagen University Hospital10, University of Copenhagen11, University of Western Australia12, Harry Perkins Institute of Medical Research13, Fiona Stanley Hospital14, University of London15, Lund University16, University of Pittsburgh17, French Institute of Health and Medical Research18, University College London19, Technische Universität München20, University of Ulm21, University of Padua22, University of Southampton23, German Cancer Research Center24, Erasmus University Medical Center25, Umeå University26, Cardiff University27, Greifswald University Hospital28, Aarhus University29, Portland State University30, University of New South Wales31, Harvard University32, National and Kapodistrian University of Athens33, University of Hawaii34, Columbia University35, University of Iowa36, Duke University37, Yamagata University38, Tuskegee University39, University of Helsinki40, University of Oulu41, Medical University of South Carolina42, Kaiser Permanente43, University of Washington44, University of Groningen45, University of Granada46, Yale University47, Prevention Institute48, University of Edinburgh49, Uppsala University50, Basque Government51, Kyushu University52, Royal Prince Alfred Hospital53, Harokopio University54, University of California, San Diego55, VU University Medical Center56, Aalborg University57, University of Eastern Finland58, Laval University59, University of Vermont60, Wake Forest Baptist Medical Center61, Wake Forest University62, Kanazawa Medical University63, Baker IDI Heart and Diabetes Institute64, Heidelberg University65, Istituto Superiore di Sanità66, Pasteur Institute67, City College of New York68, Howard University69, University of Glasgow70, International Agency for Research on Cancer71, University of Bristol72, University of Auckland73
TL;DR: Current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week, and data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
TL;DR: It is demonstrated that speed breeding in fully enclosed, controlled-environment growth chambers can accelerate plant development for research purposes, including phenotyping of adult plant traits, mutant studies and transformation.
Abstract: The growing human population and a changing environment have raised significant concern for global food security, with the current improvement rate of several important crops inadequate to meet future demand1. This slow improvement rate is attributed partly to the long generation times of crop plants. Here, we present a method called ‘speed breeding’, which greatly shortens generation time and accelerates breeding and research programmes. Speed breeding can be used to achieve up to 6 generations per year for spring wheat (Triticum aestivum), durum wheat (T. durum), barley (Hordeum vulgare), chickpea (Cicer arietinum) and pea (Pisum sativum), and 4 generations for canola (Brassica napus), instead of 2–3 under normal glasshouse conditions. We demonstrate that speed breeding in fully enclosed, controlled-environment growth chambers can accelerate plant development for research purposes, including phenotyping of adult plant traits, mutant studies and transformation. The use of supplemental lighting in a glasshouse environment allows rapid generation cycling through single seed descent (SSD) and potential for adaptation to larger-scale crop improvement programs. Cost saving through light-emitting diode (LED) supplemental lighting is also outlined. We envisage great potential for integrating speed breeding with other modern crop breeding technologies, including high-throughput genotyping, genome editing and genomic selection, accelerating the rate of crop improvement.
TL;DR: For the first time, specific loci that distinguish between BD and SCZ are discovered and polygenic components underlying multiple symptom dimensions are identified that point to the utility of genetics to inform symptomology and potential treatment.
TL;DR: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability‐free survival than a liberal fluid regimen and was associated with an increased rate of acute kidney injury.
Abstract: Background Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. Methods In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. Results During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 149...
TL;DR: In this article, a cost sensitive deep neural network (CoSen) is proposed to learn robust feature representations for both the majority and minority classes, which jointly optimizes the class-dependent costs and the neural network parameters.
Abstract: Class imbalance is a common problem in the case of real-world object detection and classification tasks. Data of some classes are abundant, making them an overrepresented majority, and data of other classes are scarce, making them an underrepresented minority. This imbalance makes it challenging for a classifier to appropriately learn the discriminating boundaries of the majority and minority classes. In this paper, we propose a cost-sensitive (CoSen) deep neural network, which can automatically learn robust feature representations for both the majority and minority classes. During training, our learning procedure jointly optimizes the class-dependent costs and the neural network parameters. The proposed approach is applicable to both binary and multiclass problems without any modification. Moreover, as opposed to data-level approaches, we do not alter the original data distribution, which results in a lower computational cost during the training process. We report the results of our experiments on six major image classification data sets and show that the proposed approach significantly outperforms the baseline algorithms. Comparisons with popular data sampling techniques and CoSen classifiers demonstrate the superior performance of our proposed method.
TL;DR: The authors argue that ecological grief is a natural and legitimate response to ecological loss, and one that may become more common as climate impacts worsen, and offer future research directions for the study of ecological grief.
Abstract: Climate change is increasingly understood to impact mental health through multiple pathways of risk, including intense feelings of grief as people suffer climate-related losses to valued species, ecosystems and landscapes. Despite growing research interest, ecologically driven grief, or ‘ecological grief’, remains an underdeveloped area of inquiry. We argue that grief is a natural and legitimate response to ecological loss, and one that may become more common as climate impacts worsen. Drawing upon our own research in Northern Canada and the Australian Wheatbelt, combined with a synthesis of the literature, we offer future research directions for the study of ecological grief. Climate change has a gradual influence on landscapes and ecosystems that may lead to feelings of loss for those with close ties to the natural environment. This Perspective describes existing research on ecological grief and outlines directions for future inquiry.
Royal Brisbane and Women's Hospital1, University of Queensland2, Princess Alexandra Hospital3, National University of Singapore4, Nanyang Technological University5, Tan Tock Seng Hospital6, Istanbul Medipol University7, King Saud bin Abdulaziz University for Health Sciences8, Sapienza University of Rome9, University of Udine10, Monash University11, American University of Beirut12, North Shore Hospital13, University of Sydney14, Westmead Hospital15, University of Cape Town16, Illawarra Health & Medical Research Institute17, University of Wollongong18, Wollongong Hospital19, Middlemore Hospital20, King Fahad Specialist Hospital21, St. Vincent's Health System22, University of Western Australia23, Fiona Stanley Hospital24, Sunnybrook Health Sciences Centre25, QIMR Berghofer Medical Research Institute26, Mater Health Services27, Deakin University28, Monash University, Clayton campus29
TL;DR: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality, and findings do not support use of piperACillin- tazobactsam in this setting.
Abstract: Importance Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective “carbapenem-sparing” option to treat extended-spectrum β-lactamase producers. Objectives To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae . Design, Setting, and Participants Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, −∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration anzctr.org.au Identifiers:ACTRN12613000532707andACTRN12615000403538and ClinicalTrials.gov Identifier:NCT02176122
TL;DR: The present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide, and is believed to be the first ever large-scale coordinated study of WM microstructural differences in schizophrenia.
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
TL;DR: NiSA-N-CNTs show an excellent selectivity and activity for the electrochemical reduction of CO2 to CO, achieving a turnover frequency (TOF) of 11.7 s-1 at -0.55 V (vs reversible hydrogen electrode (RHE)), two orders of magnitude higher than Ni nanoparticles supported on CNTs.
Abstract: Single-atom catalysts (SACs) are the smallest entities for catalytic reactions with projected high atomic efficiency, superior activity, and selectivity; however, practical applications of SACs suffer from a very low metal loading of 1-2 wt%. Here, a class of SACs based on atomically dispersed transition metals on nitrogen-doped carbon nanotubes (MSA-N-CNTs, where M = Ni, Co, NiCo, CoFe, and NiPt) is synthesized with an extraordinarily high metal loading, e.g., 20 wt% in the case of NiSA-N-CNTs, using a new multistep pyrolysis process. Among these materials, NiSA-N-CNTs show an excellent selectivity and activity for the electrochemical reduction of CO2 to CO, achieving a turnover frequency (TOF) of 11.7 s-1 at -0.55 V (vs reversible hydrogen electrode (RHE)), two orders of magnitude higher than Ni nanoparticles supported on CNTs.
The Heart Research Institute1, Saint Louis University2, Wake Forest University3, University of Maryland, Baltimore4, Heidelberg University5, University of Florida6, University of Milan7, University of Miami8, University of Erlangen-Nuremberg9, Université du Québec à Montréal10, University of Otago11, University of Adelaide12, Agostino Gemelli University Polyclinic13, United States Department of Veterans Affairs14, Tufts University15, Kyung Hee University16, Dalhousie University17, King's College London18, Sichuan University19, The Chinese University of Hong Kong20, University of Western Australia21, National Institutes of Health22, National University of Singapore23, Uppsala University24, University of São Paulo25, Memorial Hospital of South Bend26, Vrije Universiteit Brussel27, Maastricht University28, Universidad Pública de Navarra29, Centre Hospitalier Universitaire de Toulouse30
TL;DR: Evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR) are presented.
Abstract: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefitharm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
TL;DR: When compared with vaginal delivery, cesarean delivery is associated with a reduced rate of urinary incontinence and pelvic organ prolapse, but this should be weighed against the association with increased risks for fertility, future pregnancy, and long-term childhood outcomes.
Abstract: Background Cesarean birth rates continue to rise worldwide with recent (2016) reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South America. The objective of this systematic review is to describe the long-term risks and benefits of cesarean delivery for mother, baby, and subsequent pregnancies. The primary maternal outcome was pelvic floor dysfunction, the primary baby outcome was asthma, and the primary subsequent pregnancy outcome was perinatal death. Methods and findings Medline, Embase, Cochrane, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were systematically searched for published studies in human subjects (last search 25 May 2017), supplemented by manual searches. Included studies were randomized controlled trials (RCTs) and large (more than 1,000 participants) prospective cohort studies with greater than or equal to one-year follow-up comparing outcomes of women delivering by cesarean delivery and by vaginal delivery. Two assessors screened 30,327 abstracts. Studies were graded for risk of bias by two assessors using the Scottish Intercollegiate Guideline Network (SIGN) Methodology Checklist and the Risk of Bias Assessment tool for Non-Randomized Studies. Results were pooled in fixed effects meta-analyses or in random effects models when significant heterogeneity was present (I2 ≥ 40%). One RCT and 79 cohort studies (all from high income countries) were included, involving 29,928,274 participants. Compared to vaginal delivery, cesarean delivery was associated with decreased risk of urinary incontinence, odds ratio (OR) 0.56 (95% CI 0.47 to 0.66; n = 58,900; 8 studies) and pelvic organ prolapse (OR 0.29, 0.17 to 0.51; n = 39,208; 2 studies). Children delivered by cesarean delivery had increased risk of asthma up to the age of 12 years (OR 1.21, 1.11 to 1.32; n = 887,960; 13 studies) and obesity up to the age of 5 years (OR 1.59, 1.33 to 1.90; n = 64,113; 6 studies). Pregnancy after cesarean delivery was associated with increased risk of miscarriage (OR 1.17, 1.03 to 1.32; n = 151,412; 4 studies) and stillbirth (OR 1.27, 1.15 to 1.40; n = 703,562; 8 studies), but not perinatal mortality (OR 1.11, 0.89 to 1.39; n = 91,429; 2 studies). Pregnancy following cesarean delivery was associated with increased risk of placenta previa (OR 1.74, 1.62 to 1.87; n = 7,101,692; 10 studies), placenta accreta (OR 2.95, 1.32 to 6.60; n = 705,108; 3 studies), and placental abruption (OR 1.38, 1.27 to 1.49; n = 5,667,160; 6 studies). This is a comprehensive review adhering to a registered protocol, and guidelines for the Meta-analysis of Observational Studies in Epidemiology were followed, but it is based on predominantly observational data, and in some meta-analyses, between-study heterogeneity is high; therefore, causation cannot be inferred and the results should be interpreted with caution. Conclusions When compared with vaginal delivery, cesarean delivery is associated with a reduced rate of urinary incontinence and pelvic organ prolapse, but this should be weighed against the association with increased risks for fertility, future pregnancy, and long-term childhood outcomes. This information could be valuable in counselling women on mode of delivery.
Andrews University1, Australian Institute of Sport2, University of Wyoming3, Western Australian Institute of Sport4, University of Western Australia5, McMaster University6, Messiah College7, Bangor University8, German Sport University Cologne9, Vrije Universiteit Brussel10, Maastricht University Medical Centre11, University of Guelph12, World Anti-Doping Agency13, English Institute of Sport14, International Olympic Committee15
TL;DR: The appropriate use of some supplements can benefit the athlete, but others may harm the athlete’s health, performance, and/or livelihood and reputation and expert professional opinion and assistance is strongly advised before an athlete embarks on supplement use.
Abstract: Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition programme. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including (1) the management of micronutrient deficiencies, (2) supply of convenient forms of energy and macronutrients, and (3) provision of direct benefits to performance or (4) indirect benefits such as supporting intense training regimens. The appropriate use of some supplements can benefit the athlete, but others may harm the athlete's health, performance, and/or livelihood and reputation (if an antidoping rule violation results). A complete nutritional assessment should be undertaken before decisions regarding supplement use are made. Supplements claiming to directly or indirectly enhance performance are typically the largest group of products marketed to athletes, but only a few (including caffeine, creatine, specific buffering agents and nitrate) have good evidence of benefits. However, responses are affected by the scenario of use and may vary widely between individuals because of factors that include genetics, the microbiome and habitual diet. Supplements intended to enhance performance should be thoroughly trialled in training or simulated competition before being used in competition. Inadvertent ingestion of substances prohibited under the antidoping codes that govern elite sport is a known risk of taking some supplements. Protection of the athlete's health and awareness of the potential for harm must be paramount; expert professional opinion and assistance is strongly advised before an athlete embarks on supplement use.