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Showing papers by "Imperial College London published in 2017"


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

10,401 citations


Proceedings ArticleDOI
21 Jul 2017
TL;DR: SRGAN as mentioned in this paper proposes a perceptual loss function which consists of an adversarial loss and a content loss, which pushes the solution to the natural image manifold using a discriminator network that is trained to differentiate between the super-resolved images and original photo-realistic images.
Abstract: Despite the breakthroughs in accuracy and speed of single image super-resolution using faster and deeper convolutional neural networks, one central problem remains largely unsolved: how do we recover the finer texture details when we super-resolve at large upscaling factors? The behavior of optimization-based super-resolution methods is principally driven by the choice of the objective function. Recent work has largely focused on minimizing the mean squared reconstruction error. The resulting estimates have high peak signal-to-noise ratios, but they are often lacking high-frequency details and are perceptually unsatisfying in the sense that they fail to match the fidelity expected at the higher resolution. In this paper, we present SRGAN, a generative adversarial network (GAN) for image super-resolution (SR). To our knowledge, it is the first framework capable of inferring photo-realistic natural images for 4x upscaling factors. To achieve this, we propose a perceptual loss function which consists of an adversarial loss and a content loss. The adversarial loss pushes our solution to the natural image manifold using a discriminator network that is trained to differentiate between the super-resolved images and original photo-realistic images. In addition, we use a content loss motivated by perceptual similarity instead of similarity in pixel space. Our deep residual network is able to recover photo-realistic textures from heavily downsampled images on public benchmarks. An extensive mean-opinion-score (MOS) test shows hugely significant gains in perceptual quality using SRGAN. The MOS scores obtained with SRGAN are closer to those of the original high-resolution images than to those obtained with any state-of-the-art method.

6,884 citations


Journal ArticleDOI
TL;DR: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence‐based interventions to address this problem.
Abstract: BACKGROUND Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHOD ...

4,519 citations


Journal ArticleDOI
TL;DR: Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls, and by contrast, the rise in BMI has accelerated in east and south Asia forboth sexes, and southeast Asia for boys.

4,317 citations


Journal ArticleDOI
TL;DR: In this trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events.
Abstract: BackgroundEvolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. MethodsWe conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. ResultsAt 48 weeks, the ...

3,810 citations


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.

2,995 citations


Journal ArticleDOI
TL;DR: In this paper, the authors show that it is possible to train networks that can maintain expertise on tasks that they have not experienced for a long time by selectively slowing down learning on the weights important for those tasks.
Abstract: The ability to learn tasks in a sequential fashion is crucial to the development of artificial intelligence. Until now neural networks have not been capable of this and it has been widely thought that catastrophic forgetting is an inevitable feature of connectionist models. We show that it is possible to overcome this limitation and train networks that can maintain expertise on tasks that they have not experienced for a long time. Our approach remembers old tasks by selectively slowing down learning on the weights important for those tasks. We demonstrate our approach is scalable and effective by solving a set of classification tasks based on a hand-written digit dataset and by learning several Atari 2600 games sequentially.

2,917 citations


Journal ArticleDOI
TL;DR: An efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data, and improves on the state-of-the‐art for all three applications.

2,842 citations


Journal ArticleDOI
TL;DR: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden, finding that CVDs remain a major cause of health loss for all regions of the world.

2,525 citations


Journal ArticleDOI
TL;DR: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
Abstract: Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).

2,003 citations


Journal ArticleDOI
TL;DR: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice and the stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment.

Journal ArticleDOI
Seth Flaxman1, Rupert R A Bourne2, Serge Resnikoff3, Serge Resnikoff4, Peter Ackland5, Tasanee Braithwaite6, Maria V Cicinelli, Aditi Das7, Jost B. Jonas8, Jill E Keeffe9, John H. Kempen10, Janet L Leasher11, Hans Limburg, Kovin Naidoo12, Kovin Naidoo4, Konrad Pesudovs13, Alexander J Silvester, Gretchen A Stevens14, Nina Tahhan3, Nina Tahhan4, Tien Yin Wong15, Hugh R. Taylor16, Rupert R A Bourne2, Aries Arditi, Yaniv Barkana, Banu Bozkurt17, Alain M. Bron, Donald L. Budenz18, Feng Cai, Robert J Casson19, Usha Chakravarthy20, Jaewan Choi, Maria Vittoria Cicinelli, Nathan Congdon20, Reza Dana21, Rakhi Dandona22, Lalit Dandona23, Iva Dekaris, Monte A. Del Monte24, Jenny deva25, Laura E. Dreer26, Leon B. Ellwein27, Marcela Frazier26, Kevin D. Frick28, David S. Friedman28, João M. Furtado29, H. Gao30, Gus Gazzard31, Ronnie George32, Stephen Gichuhi33, Victor H. Gonzalez, Billy R. Hammond34, Mary Elizabeth Hartnett35, Minguang He16, James F. Hejtmancik, Flavio E. Hirai36, John J Huang37, April D. Ingram38, Jonathan C. Javitt28, Jost B. Jonas8, Charlotte E. Joslin39, John H Kempen10, Moncef Khairallah, Rohit C Khanna9, Judy E. Kim40, George N. Lambrou41, Van C. Lansingh, Paolo Lanzetta42, Jennifer I. Lim43, Kaweh Mansouri, Anu A. Mathew44, Alan R. Morse, Beatriz Munoz, David C. Musch24, Vinay Nangia, Maria Palaiou10, Maurizio Battaglia Parodi, Fernando Yaacov Pena, Tunde Peto20, Harry A. Quigley, Murugesan Raju45, Pradeep Y. Ramulu46, Zane Rankin15, Dana Reza21, Alan L. Robin23, Luca Rossetti47, Jinan B. Saaddine46, Mya Sandar15, Janet B. Serle48, Tueng T. Shen23, Rajesh K. Shetty49, Pamela C. Sieving27, Juan Carlos Silva50, Rita S. Sitorus51, Dwight Stambolian52, Gretchen Stevens14, Hugh Taylor16, Jaime Tejedor, James M. Tielsch28, Miltiadis K. Tsilimbaris53, Jan C. van Meurs, Rohit Varma54, Gianni Virgili55, Ya Xing Wang56, Ningli Wang56, Sheila K. West, Peter Wiedemann57, Tien Wong15, Richard Wormald6, Yingfeng Zheng15 
Imperial College London1, Anglia Ruskin University2, University of New South Wales3, Brien Holden Vision Institute4, International Agency for the Prevention of Blindness5, Moorfields Eye Hospital6, York Hospital7, Heidelberg University8, L V Prasad Eye Institute9, Massachusetts Eye and Ear Infirmary10, Nova Southeastern University11, University of KwaZulu-Natal12, National Health and Medical Research Council13, World Health Organization14, National University of Singapore15, University of Melbourne16, Selçuk University17, University of Miami18, University of Adelaide19, Queen's University Belfast20, Harvard University21, The George Institute for Global Health22, University of Washington23, University of Michigan24, Universiti Tunku Abdul Rahman25, University of Alabama at Birmingham26, National Institutes of Health27, Johns Hopkins University28, University of São Paulo29, Henry Ford Health System30, University College London31, Sankara Nethralaya32, University of Nairobi33, University of Georgia34, University of Utah35, Federal University of São Paulo36, Yale University37, Alberta Children's Hospital38, University of Illinois at Chicago39, Medical College of Wisconsin40, Novartis41, University of Udine42, University of Illinois at Urbana–Champaign43, Royal Children's Hospital44, University of Missouri45, Centers for Disease Control and Prevention46, University of Milan47, Icahn School of Medicine at Mount Sinai48, Mayo Clinic49, Pan American Health Organization50, University of Indonesia51, University of Pennsylvania52, University of Crete53, University of Southern California54, University of Florence55, Capital Medical University56, Leipzig University57
TL;DR: A series of regression models were fitted to estimate the proportion of moderate or severe vision impairment and blindness by cause, age, region, and year, and found that world regions varied markedly in the causes of blindness and vision impairment in this age group.

Journal ArticleDOI
D. S. Akerib1, S. Alsum2, Henrique Araujo3, X. Bai4, A. J. Bailey3, J. Balajthy5, P. Beltrame, Ethan Bernard6, A. Bernstein7, T. P. Biesiadzinski1, E. M. Boulton6, R. Bramante1, P. Brás8, D. Byram9, Sidney Cahn10, M. C. Carmona-Benitez11, C. Chan12, A.A. Chiller9, C. Chiller9, A. Currie3, J. E. Cutter13, T. J. R. Davison, A. Dobi14, J. E. Y. Dobson15, E. Druszkiewicz16, B. N. Edwards10, C. H. Faham14, S. Fiorucci12, R. J. Gaitskell12, V. M. Gehman14, C. Ghag15, K.R. Gibson1, M. G. D. Gilchriese14, C. R. Hall5, M. Hanhardt4, S. J. Haselschwardt11, S. A. Hertel6, D. P. Hogan6, M. Horn6, D. Q. Huang12, C. M. Ignarra17, M. Ihm6, R.G. Jacobsen6, W. Ji1, K. Kamdin6, K. Kazkaz7, D. Khaitan16, R. Knoche5, N.A. Larsen10, C. Lee1, B. G. Lenardo7, K. T. Lesko14, A. Lindote8, M.I. Lopes8, A. Manalaysay13, R. L. Mannino18, M. F. Marzioni, Daniel McKinsey6, D. M. Mei9, J. Mock19, M. Moongweluwan16, J. A. Morad13, A. St. J. Murphy20, C. Nehrkorn11, H. N. Nelson11, F. Neves8, K. O’Sullivan6, K. C. Oliver-Mallory6, K. J. Palladino17, E. K. Pease6, P. Phelps1, L. Reichhart15, C. Rhyne12, S. Shaw15, T. A. Shutt1, C. Silva8, M. Solmaz11, V. N. Solovov8, P. Sorensen14, S. Stephenson13, T. J. Sumner3, Matthew Szydagis19, D. J. Taylor, W. C. Taylor12, B. P. Tennyson10, P. A. Terman18, D. R. Tiedt4, W. H. To1, Mani Tripathi13, L. Tvrznikova6, S. Uvarov13, J.R. Verbus12, R. C. Webb18, J. T. White18, T. J. Whitis1, M. S. Witherell14, F.L.H. Wolfs16, Jilei Xu7, K. Yazdani3, Sarah Young19, Chao Zhang9 
TL;DR: This search yields no evidence of WIMP nuclear recoils and constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon experiment are reported.
Abstract: We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

Journal ArticleDOI
TL;DR: Deep reinforcement learning (DRL) is poised to revolutionize the field of artificial intelligence (AI) and represents a step toward building autonomous systems with a higher-level understanding of the visual world as discussed by the authors.
Abstract: Deep reinforcement learning (DRL) is poised to revolutionize the field of artificial intelligence (AI) and represents a step toward building autonomous systems with a higherlevel understanding of the visual world. Currently, deep learning is enabling reinforcement learning (RL) to scale to problems that were previously intractable, such as learning to play video games directly from pixels. DRL algorithms are also applied to robotics, allowing control policies for robots to be learned directly from camera inputs in the real world. In this survey, we begin with an introduction to the general field of RL, then progress to the main streams of value-based and policy-based methods. Our survey will cover central algorithms in deep RL, including the deep Q-network (DQN), trust region policy optimization (TRPO), and asynchronous advantage actor critic. In parallel, we highlight the unique advantages of deep neural networks, focusing on visual understanding via RL. To conclude, we describe several current areas of research within the field.

Journal ArticleDOI
TL;DR: This 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies.

Journal ArticleDOI
Bin Zhou1, James Bentham1, Mariachiara Di Cesare2, Honor Bixby1  +787 moreInstitutions (231)
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.

Proceedings ArticleDOI
10 Jan 2017
TL;DR: The authors describe an open-source toolkit for neural machine translation (NMT) that prioritizes efficiency, modularity, and extensibility with the goal of supporting NMT research into model architectures, feature representations, and source modalities.
Abstract: We describe an open-source toolkit for neural machine translation (NMT). The toolkit prioritizes efficiency, modularity, and extensibility with the goal of supporting NMT research into model architectures, feature representations, and source modalities, while maintaining competitive performance and reasonable training requirements. The toolkit consists of modeling and translation support, as well as detailed pedagogical documentation about the underlying techniques.

Journal ArticleDOI
TL;DR: This systematic review of interventions to improve antibiotic prescribing to hospital inpatients showed interventions to be associated with improvement in prescribing according to antibiotic policy in routine clinical practice, with 70% of interventions being hospital-wide compared with 31% for RCTs.
Abstract: BACKGROUND: Antibiotic resistance is a major public health problem. Infections caused by multidrug-resistant bacteria are associated with prolonged hospital stay and death compared with infections caused by susceptible bacteria. Appropriate antibiotic use in hospitals should ensure effective treatment of patients with infection and reduce unnecessary prescriptions. We updated this systematic review to evaluate the impact of interventions to improve antibiotic prescribing to hospital inpatients. OBJECTIVES: To estimate the effectiveness and safety of interventions to improve antibiotic prescribing to hospital inpatients and to investigate the effect of two intervention functions: restriction and enablement. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, and Embase. We searched for additional studies using the bibliographies of included articles and personal files. The last search from which records were evaluated and any studies identified incorporated into the review was January 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies (NRS). We included three non-randomised study designs to measure behavioural and clinical outcomes and analyse variation in the effects: non- randomised trials (NRT), controlled before-after (CBA) studies and interrupted time series (ITS) studies. For this update we also included three additional NRS designs (case control, cohort, and qualitative studies) to identify unintended consequences. Interventions included any professional or structural interventions as defined by the Cochrane Effective Practice and Organisation of Care Group. We defined restriction as 'using rules to reduce the opportunity to engage in the target behaviour (or increase the target behaviour by reducing the opportunity to engage in competing behaviours)'. We defined enablement as 'increasing means/reducing barriers to increase capability or opportunity'. The main comparison was between intervention and no intervention. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and assessed study risk of bias. We performed meta-analysis and meta-regression of RCTs and meta-regression of ITS studies. We classified behaviour change functions for all interventions in the review, including those studies in the previously published versions. We analysed dichotomous data with a risk difference (RD). We assessed certainty of evidence with GRADE criteria. MAIN RESULTS: This review includes 221 studies (58 RCTs, and 163 NRS). Most studies were from North America (96) or Europe (87). The remaining studies were from Asia (19), South America (8), Australia (8), and the East Asia (3). Although 62% of RCTs were at a high risk of bias, the results for the main review outcomes were similar when we restricted the analysis to studies at low risk of bias.More hospital inpatients were treated according to antibiotic prescribing policy with the intervention compared with no intervention based on 29 RCTs of predominantly enablement interventions (RD 15%, 95% confidence interval (CI) 14% to 16%; 23,394 participants; high-certainty evidence). This represents an increase from 43% to 58% .There were high levels of heterogeneity of effect size but the direction consistently favoured intervention.The duration of antibiotic treatment decreased by 1.95 days (95% CI 2.22 to 1.67; 14 RCTs; 3318 participants; high-certainty evidence) from 11.0 days. Information from non-randomised studies showed interventions to be associated with improvement in prescribing according to antibiotic policy in routine clinical practice, with 70% of interventions being hospital-wide compared with 31% for RCTs. The risk of death was similar between intervention and control groups (11% in both arms), indicating that antibiotic use can likely be reduced without adversely affecting mortality (RD 0%, 95% CI -1% to 0%; 28 RCTs; 15,827 participants; moderate-certainty evidence). Antibiotic stewardship interventions probably reduce length of stay by 1.12 days (95% CI 0.7 to 1.54 days; 15 RCTs; 3834 participants; moderate-certainty evidence). One RCT and six NRS raised concerns that restrictive interventions may lead to delay in treatment and negative professional culture because of breakdown in communication and trust between infection specialists and clinical teams (low-certainty evidence).Both enablement and restriction were independently associated with increased compliance with antibiotic policies, and enablement enhanced the effect of restrictive interventions (high-certainty evidence). Enabling interventions that included feedback were probably more effective than those that did not (moderate-certainty evidence).There was very low-certainty evidence about the effect of the interventions on reducing Clostridium difficile infections (median -48.6%, interquartile range -80.7% to -19.2%; 7 studies). This was also the case for resistant gram-negative bacteria (median -12.9%, interquartile range -35.3% to 25.2%; 11 studies) and resistant gram-positive bacteria (median -19.3%, interquartile range -50.1% to +23.1%; 9 studies). There was too much variance in microbial outcomes to reliably assess the effect of change in antibiotic use. Heterogeneity of intervention effect on prescribing outcomesWe analysed effect modifiers in 29 RCTs and 91 ITS studies. Enablement and restriction were independently associated with a larger effect size (high-certainty evidence). Feedback was included in 4 (17%) of 23 RCTs and 20 (47%) of 43 ITS studies of enabling interventions and was associated with greater intervention effect. Enablement was included in 13 (45%) of 29 ITS studies with restrictive interventions and enhanced intervention effect. AUTHORS' CONCLUSIONS: We found high-certainty evidence that interventions are effective in increasing compliance with antibiotic policy and reducing duration of antibiotic treatment. Lower use of antibiotics probably does not increase mortality and likely reduces length of stay. Additional trials comparing antibiotic stewardship with no intervention are unlikely to change our conclusions. Enablement consistently increased the effect of interventions, including those with a restrictive component. Although feedback further increased intervention effect, it was used in only a minority of enabling interventions. Interventions were successful in safely reducing unnecessary antibiotic use in hospitals, despite the fact that the majority did not use the most effective behaviour change techniques. Consequently, effective dissemination of our findings could have considerable health service and policy impact. Future research should instead focus on targeting treatment and assessing other measures of patient safety, assess different stewardship interventions, and explore the barriers and facilitators to implementation. More research is required on unintended consequences of restrictive interventions.

Journal ArticleDOI
TL;DR: The methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn’s disease of this ECCO Consensus are concerns.
Abstract: This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016].

Journal ArticleDOI
TL;DR: Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality, and public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular Disease, cancer, and premature mortality are supported.
Abstract: Background Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations. Methods PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included. Results For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90-0.94, I 2 = 0%, n = 15] for coronary heart disease, 0.84 (95% CI: 0.76-0.92, I 2 = 73%, n = 10) for stroke, 0.92 (95% CI: 0.90-0.95, I 2 = 31%, n = 13) for cardiovascular disease, 0.97 (95% CI: 0.95-0.99, I 2 = 49%, n = 12) for total cancer and 0.90 (95% CI: 0.87-0.93, I 2 = 83%, n = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal. Conclusions Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality.

Journal ArticleDOI
01 Jan 2017
TL;DR: A comprehensive up-to-date review of research employing deep learning in health informatics is presented, providing a critical analysis of the relative merit, and potential pitfalls of the technique as well as its future outlook.
Abstract: With a massive influx of multimodality data, the role of data analytics in health informatics has grown rapidly in the last decade. This has also prompted increasing interests in the generation of analytical, data driven models based on machine learning in health informatics. Deep learning, a technique with its foundation in artificial neural networks, is emerging in recent years as a powerful tool for machine learning, promising to reshape the future of artificial intelligence. Rapid improvements in computational power, fast data storage, and parallelization have also contributed to the rapid uptake of the technology in addition to its predictive power and ability to generate automatically optimized high-level features and semantic interpretation from the input data. This article presents a comprehensive up-to-date review of research employing deep learning in health informatics, providing a critical analysis of the relative merit, and potential pitfalls of the technique as well as its future outlook. The paper mainly focuses on key applications of deep learning in the fields of translational bioinformatics, medical imaging, pervasive sensing, medical informatics, and public health.

Journal ArticleDOI
Andrew I R Maas1, David K. Menon2, P. David Adelson3, Nada Andelic4  +339 moreInstitutions (110)
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators

Journal ArticleDOI
TL;DR: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo.
Abstract: BackgroundThe cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. MethodsWe randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. ResultsIn all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2...

Journal ArticleDOI
TL;DR: It is shown that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration and enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice, and Amuc_1100, a specific protein isolated from the outer membrane of A. Sydneyi, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization and partly recapitulates the beneficial effects of the bacterium.
Abstract: Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.

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TL;DR: This research presents a meta-analyses of Gastroenterology and Hepatology at the cellular and molecular level, which shows clear trends in the development of immune-oncology-metabolical pathways towards “clinically checkpoints”.
Abstract: aDepartment of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal bIBD Unit, DIMEC, University of Bologna, Bologna, Italy cDepartment of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel dGastrointestinal Unit ASST Fatebenefratelli Sacco—University of Milan—Milan, Italy eIBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita’ Cattolica del Sacro Cuore, Rome, Italy fDepartment of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain gDepartment of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark hFirst Department of Medicine, Semmelweis University, Budapest, Hungary iIBD Unit, St Mark’s Hospital, Middlesex, UK jDepartment of Gastroenterology, University Hospital of Ghent, Ghent, Belgium kInstitute of Pathology, Medical University of Graz, Graz, Austria lDepartment of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK mUnit of General Surgery, Second University of Naples, Napoli, Italy nMaria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland oDepartment of Medicine, University of Cambridge, Cambridge, UK pImperial College London; Chelsea and Westminster Hospital, London, UK qDepartment of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

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Tomi Akinyemiju1, Semaw Ferede Abera2, Semaw Ferede Abera3, Muktar Beshir Ahmed4, Noore Alam5, Noore Alam6, Mulubirhan Assefa Alemayohu7, Christine Allen8, Rajaa Al-Raddadi, Nelson Alvis-Guzman9, Yaw Ampem Amoako10, Al Artaman11, Tadesse Awoke Ayele12, Aleksandra Barac, Isabela M. Benseñor13, Adugnaw Berhane2, Zulfiqar A Bhutta14, Jacqueline Castillo-Rivas, Abdulaal A Chitheer, Jee-Young Choi15, Benjamin C Cowie, Lalit Dandona8, Lalit Dandona16, Rakhi Dandona8, Rakhi Dandona16, Subhojit Dey, Daniel Dicker8, Huyen Do Phuc17, Donatus U. Ekwueme18, Maysaa El Sayed Zaki, Florian Fischer19, Thomas Fürst20, Thomas Fürst21, Thomas Fürst22, Jamie Hancock8, Simon I. Hay8, Peter J. Hotez23, Peter J. Hotez24, Sun Ha Jee25, Amir Kasaeian26, Yousef Khader27, Young-Ho Khang15, G Anil Kumar16, Michael Kutz8, Heidi J. Larson28, Alan D. Lopez29, Alan D. Lopez8, Raimundas Lunevicius30, Raimundas Lunevicius31, Reza Malekzadeh26, Colm McAlinden, Toni Meier32, Walter Mendoza33, Ali H. Mokdad8, Maziar Moradi-Lakeh34, Gabriele Nagel35, Quyen Nguyen17, Grant Nguyen8, Felix Akpojene Ogbo36, George C Patton29, David M. Pereira37, Farshad Pourmalek38, Mostafa Qorbani, Amir Radfar39, Gholamreza Roshandel40, Joshua A. Salomon41, Juan Sanabria42, Juan Sanabria43, Benn Sartorius44, Maheswar Satpathy45, Maheswar Satpathy46, Monika Sawhney42, Sadaf G. Sepanlou26, Katya Anne Shackelford8, Hirbo Shore47, Jiandong Sun48, Desalegn Tadese Mengistu7, Roman Topór-Mądry49, Roman Topór-Mądry50, Bach Xuan Tran51, Bach Xuan Tran52, Kingsley N. Ukwaja, Vasiliy Victorovich Vlassov53, Stein Emil Vollset54, Stein Emil Vollset55, Theo Vos8, Tolassa Wakayo4, Elisabete Weiderpass56, Elisabete Weiderpass57, Andrea Werdecker, Naohiro Yonemoto58, Mustafa Z. Younis59, Mustafa Z. Younis41, Chuanhua Yu60, Zoubida Zaidi, Liguo Zhu18, Christopher J L Murray8, Mohsen Naghavi8, Christina Fitzmaurice8, Christina Fitzmaurice61 
University of Alabama at Birmingham1, College of Health Sciences, Bahrain2, University of Hohenheim3, Jimma University4, University of Queensland5, Queensland Government6, Mekelle University7, Institute for Health Metrics and Evaluation8, University of Cartagena9, Komfo Anokye Teaching Hospital10, University of Manitoba11, University of Gondar12, University of São Paulo13, Aga Khan University14, New Generation University College15, Public Health Foundation of India16, Duy Tan University17, Centers for Disease Control and Prevention18, Bielefeld University19, University of Basel20, Imperial College London21, Swiss Tropical and Public Health Institute22, Boston Children's Hospital23, Baylor College of Medicine24, Yonsei University25, Tehran University of Medical Sciences26, Jordan University of Science and Technology27, University of London28, University of Melbourne29, University of Liverpool30, Aintree University Hospitals NHS Foundation Trust31, Martin Luther University of Halle-Wittenberg32, United Nations Population Fund33, Iran University of Medical Sciences34, University of Ulm35, University of Sydney36, University of Porto37, University of British Columbia38, A.T. Still University39, Golestan University40, Harvard University41, Marshall University42, Case Western Reserve University43, University of KwaZulu-Natal44, Utkal University45, AIIMS, New Delhi46, Haramaya University47, Queensland University of Technology48, Wrocław Medical University49, Jagiellonian University Medical College50, Johns Hopkins University51, Hanoi Medical University52, National Research University – Higher School of Economics53, Norwegian Institute of Public Health54, University of Bergen55, Karolinska Institutet56, University of Tromsø57, Kyoto University58, Jackson State University59, Wuhan University60, University of Washington61
TL;DR: In this article, the authors report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol, and an “other” group that encompasses residual causes.
Abstract: Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.

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TL;DR: This Review summarizes the main processes and new mechanisms involved in the formation of the pre-metastatic niche and describes the main mechanisms used to modify organs of future metastasis.
Abstract: It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

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TL;DR: It is demonstrated that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients and achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach.
Abstract: Single-cell RNA-seq enables the quantitative characterization of cell types based on global transcriptome profiles. We present single-cell consensus clustering (SC3), a user-friendly tool for unsupervised clustering, which achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach (http://bioconductor.org/packages/SC3). We demonstrate that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients.

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TL;DR: In this paper, the authors present expert views on future capital cost, lifetime and efficiency for three electrolysis technologies: alkaline (AEC), proton exchange membrane (PEMEC) and solid oxide electrolysis cell (SOEC).

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TL;DR: The 2017 roadmap of terahertz frequency electromagnetic radiation (100 GHz-30 THz) as discussed by the authors provides a snapshot of the present state of THz science and technology in 2017, and provides an opinion on the challenges and opportunities that the future holds.
Abstract: Science and technologies based on terahertz frequency electromagnetic radiation (100 GHz–30 THz) have developed rapidly over the last 30 years. For most of the 20th Century, terahertz radiation, then referred to as sub-millimeter wave or far-infrared radiation, was mainly utilized by astronomers and some spectroscopists. Following the development of laser based terahertz time-domain spectroscopy in the 1980s and 1990s the field of THz science and technology expanded rapidly, to the extent that it now touches many areas from fundamental science to 'real world' applications. For example THz radiation is being used to optimize materials for new solar cells, and may also be a key technology for the next generation of airport security scanners. While the field was emerging it was possible to keep track of all new developments, however now the field has grown so much that it is increasingly difficult to follow the diverse range of new discoveries and applications that are appearing. At this point in time, when the field of THz science and technology is moving from an emerging to a more established and interdisciplinary field, it is apt to present a roadmap to help identify the breadth and future directions of the field. The aim of this roadmap is to present a snapshot of the present state of THz science and technology in 2017, and provide an opinion on the challenges and opportunities that the future holds. To be able to achieve this aim, we have invited a group of international experts to write 18 sections that cover most of the key areas of THz science and technology. We hope that The 2017 Roadmap on THz science and technology will prove to be a useful resource by providing a wide ranging introduction to the capabilities of THz radiation for those outside or just entering the field as well as providing perspective and breadth for those who are well established. We also feel that this review should serve as a useful guide for government and funding agencies.