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Showing papers by "University of Leeds published in 2019"



Journal ArticleDOI
TL;DR: This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase.
Abstract: Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.

1,394 citations


Journal ArticleDOI
01 Jan 2019-Pain
TL;DR: In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in this proposal, this subgroup is called “chronic primary pain,” and in 6 other subgroups, pain is secondary to an underlying disease.
Abstract: Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.

1,311 citations


Journal ArticleDOI
27 Sep 2019-Gut
TL;DR: Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care.
Abstract: Ulcerative colitis and Crohn’s disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn’s and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn’s disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn’s disease, including patients, their families and friends.

1,140 citations


Journal ArticleDOI
07 Nov 2019-Nature
TL;DR: The capture and use of carbon dioxide to create valuable products might lower the net costs of reducing emissions or removing carbon dioxide from the atmosphere, but barriers to implementation remain substantial and resource constraints prevent the simultaneous deployment of all pathways.
Abstract: The capture and use of carbon dioxide to create valuable products might lower the net costs of reducing emissions or removing carbon dioxide from the atmosphere. Here we review ten pathways for the utilization of carbon dioxide. Pathways that involve chemicals, fuels and microalgae might reduce emissions of carbon dioxide but have limited potential for its removal, whereas pathways that involve construction materials can both utilize and remove carbon dioxide. Land-based pathways can increase agricultural output and remove carbon dioxide. Our assessment suggests that each pathway could scale to over 0.5 gigatonnes of carbon dioxide utilization annually. However, barriers to implementation remain substantial and resource constraints prevent the simultaneous deployment of all pathways. Ten pathways for the utilization of carbon dioxide are reviewed, considering their potential scale, economics and barriers to implementation.

879 citations


Journal ArticleDOI
TL;DR: It is shown that deep residual learning can predict MSI directly from H&E histology, which is ubiquitously available and has the potential to provide immunotherapy to a much broader subset of patients with gastrointestinal cancer.
Abstract: Microsatellite instability determines whether patients with gastrointestinal cancer respond exceptionally well to immunotherapy. However, in clinical practice, not every patient is tested for MSI, because this requires additional genetic or immunohistochemical tests. Here we show that deep residual learning can predict MSI directly from H&E histology, which is ubiquitously available. This approach has the potential to provide immunotherapy to a much broader subset of patients with gastrointestinal cancer.

705 citations


Journal ArticleDOI
TL;DR: This randomised, controlled, multicentre, phase 3 study aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.
Abstract: BACKGROUND Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer. METHODS This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13. FINDINGS Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37-60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6-59·1) in the capecitabine group compared with 36·4 months (29·7-44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55-0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30-44) in the observation group (adjusted HR 0·75, 95% CI 0·58-0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6-35·9) in the capecitabine group and 17·5 months (12·0-23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8-46·3) in the capecitabine group and 17·4 months (12·0-23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related. INTERPRETATION Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting. FUNDING Cancer Research UK and Roche.

652 citations


Journal ArticleDOI
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

606 citations


Journal ArticleDOI
TL;DR: In this article, a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts is described. But despite the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work.
Abstract: This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.

469 citations


Journal ArticleDOI
TL;DR: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year after randomization.
Abstract: Background The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninfer...

460 citations


Journal ArticleDOI
01 Jan 2019-Pain
TL;DR: The most common conditions of peripheral neuropathic pain are trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neural gia, and painful radiculopathy.
Abstract: The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.

Journal ArticleDOI
TL;DR: The United Kingdom Earth System Model UKESM1 as discussed by the authors was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components.
Abstract: We document the development of the first version of the United Kingdom Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include: a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall the model performs well, with a stable pre‐industrial state, and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealised simulations show a high climate sensitivity relative to previous generations of models: equilibrium climate sensitivity (ECS) is 5.4 K, transient climate response (TCR) ranges from 2.68 K to 2.85 K, and transient climate response to cumulative emissions (TCRE) is 2.49 K/TtC to 2.66 K/TtC.

Journal ArticleDOI
TL;DR: In this paper, a review of emerging supplementary cementitious materials (SCM) sources is presented, along with new developments in characterizing and qualifying SCMs for use and improved knowledge of SCM on long-term concrete performance and durability.

Journal ArticleDOI
TL;DR: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD) aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice.
Abstract: Aim: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD), initiated by the European Academy of Childhood Disability (EACD), aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice. Method: Key questions in five areas were considered through literature reviews and formal expert consensus. For recommendations based on evidence, literature searches on ‘mechanisms’, ‘assessment’, and ‘intervention’ were updated since the last recommendations in 2012. New searches were conducted for ‘psychosocial issues’ and ‘adolescents/adults’. Evidence was rated according to the Oxford Centre for Evidence-Based Medicine (level of evidence [LOE] 1–4) and transferred into recommendations. For recommendations based on formal consensus, two meetings of an international, multidisciplinary expert panel were conducted with a further five Delphi rounds to develop good clinical practice (GCP) recommendations. Results: Thirty-five recommendations were made. Eight were based on the evidence from literature reviews (three on ‘assessment’, five on ‘intervention’). Twenty-two were updated from the 2012 recommendations. New recommendations relate to diagnosis and assessment (two GCPs) and psychosocial issues (three GCPs). Additionally, one new recommendation (LOE) reflects active video games as adjuncts to more traditional activity-oriented and participation-oriented interventions, and two new recommendations (one GCP, one LOE) were made for adolescents and adults with DCD. Interpretation: The CPR–DCD is a comprehensive overview of DCD and current understanding based on research evidence and expert consensus. It reflects the state of the art for clinicians and scientists of varied disciplines. The international CPR–DCD may serve as a basis for national guidelines. What this paper adds: Updated international clinical practice guidelines on developmental coordination disorder (DCD). Refined and extended recommendations on clinical assessment and intervention for DCD. A critical synopsis of current research on mechanisms of DCD. A critical synopsis of psychosocial issues in DCD, with implications for clinical practice. The first international recommendations to consider adolescents and adults with DCD.

Journal ArticleDOI
TL;DR: Quantum cryptography is arguably the fastest growing area in quantum information science as mentioned in this paper, and many quantum key distribution protocols have been proposed, both theoretically and experimentally, over the last few decades.
Abstract: Quantum cryptography is arguably the fastest growing area in quantum information science. Novel theoretical protocols are designed on a regular basis, security proofs are constantly improving, and experiments are gradually moving from proof-of-principle lab demonstrations to in-field implementations and technological prototypes. In this review, we provide both a general introduction and a state of the art description of the recent advances in the field, both theoretically and experimentally. We start by reviewing protocols of quantum key distribution based on discrete variable systems. Next we consider aspects of device independence, satellite challenges, and high rate protocols based on continuous variable systems. We will then discuss the ultimate limits of point-to-point private communications and how quantum repeaters and networks may overcome these restrictions. Finally, we will discuss some aspects of quantum cryptography beyond standard quantum key distribution, including quantum data locking and quantum digital signatures.

Journal ArticleDOI
TL;DR: Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.
Abstract: To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Journal ArticleDOI
TL;DR: The indicator film can be used to monitor pork freshness for intelligent packaging and showed visible changes from red to green when employed to monitor the freshness of pork stored at 25 °C, before the TVB-N value of the pork gradually increased to the rejection limit.

Journal ArticleDOI
TL;DR: An introduction to Apollo, a powerful new freeware package for R that aims to provide a comprehensive set of modelling tools for both new and experienced users, which incorporates numerous post-estimation tools.
Abstract: The community of choice modellers has expanded substantially over recent years, covering many disciplines and encompassing users with very different levels of econometric and computational skills. This paper presents an introduction to Apollo, a powerful new freeware package for R that aims to provide a comprehensive set of modelling tools for both new and experienced users. Apollo also incorporates numerous post-estimation tools, allows for both classical and Bayesian estimation, and permits advanced users to develop their own routines for new model structures.

Journal ArticleDOI
TL;DR: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013, suggesting a doubling in incidence rate within approximately 20 years in Europe.
Abstract: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004–2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

Journal ArticleDOI
TL;DR: A 32-multi-model ensemble is tested and applied to simulate global wheat yield and quality in a changing climate to potential benefits of elevated atmospheric CO2 concentration by 2050, likely to be negated by impacts from rising temperature and changes in rainfall, but with considerable disparities between regions.
Abstract: Wheat grain protein concentration is an important determinant of wheat quality for human nutrition that is often overlooked in efforts to improve crop production. We tested and applied a 32‐multi‐model ensemble to simulate global wheat yield and quality in a changing climate. Potential benefits of elevated atmospheric CO2 concentration by 2050 on global wheat grain and protein yield are likely to be negated by impacts from rising temperature and changes in rainfall, but with considerable disparities between regions. Grain and protein yields are expected to be lower and more variable in most low‐rainfall regions, with nitrogen availability limiting growth stimulus from elevated CO2. Introducing genotypes adapted to warmer temperatures (and also considering changes in CO2 and rainfall) could boost global wheat yield by 7% and protein yield by 2%, but grain protein concentration would be reduced by −1.1 percentage points, representing a relative change of −8.6%. Climate change adaptations that benefit grain yield are not always positive for grain quality, putting additional pressure on global wheat production.

Journal ArticleDOI
TL;DR: Brockway et al. as discussed by the authors calculated global time series (1995-2011) energy-return-on-investment ratios for fossil fuels at both primary and final energy stages and found very low ratios at the final stage: around 6:1 and declining.
Abstract: Under many scenarios, fossil fuels are projected to remain the dominant energy source until at least 2050. However, harder-to-reach fossil fuels require more energy to extract and, hence, are coming at an increasing ‘energy cost’. Associated declines in fossil fuel energy-return-on-investment ratios at first appear of little concern, given that published estimates for oil, coal and gas are typically above 25:1. However, such ratios are measured at the primary energy stage and should instead be estimated at the final stage where energy enters the economy (for example, electricity and petrol). Here, we calculate global time series (1995–2011) energy-return-on-investment ratios for fossil fuels at both primary and final energy stages. We concur with common primary-stage estimates (~30:1), but find very low ratios at the final stage: around 6:1 and declining. This implies that fossil fuel energy-return-on-investment ratios may be much closer to those of renewables than previously expected and that they could decline precipitously in the near future. Published energy-return-on-investment ratios for fossil fuels have not always been estimated at the final point of use. By including all energy required for processing and the supply chain, Brockway et al. find that fossil fuels might have final energy return close to renewables and susceptible to rapid further decline in the near future.

Journal ArticleDOI
TL;DR: A weak quasilocal deformation of the Rydberg-blockaded Hamiltonian is constructed, which makes the revivals virtually perfect and suggests the existence of an underlying nonintegrable Hamiltonian which supports an emergent SU(2)-spin dynamics within a small subspace of the many-body Hilbert space.
Abstract: Motivated by recent experimental observations of coherent many-body revivals in a constrained Rydberg atom chain, we construct a weak quasi-local deformation of the Rydberg blockade Hamiltonian, which makes the revivals virtually perfect. Our analysis suggests the existence of an underlying non-integrable Hamiltonian which supports an emergent SU(2)-spin dynamics within a small subspace of the many-body Hilbert space. We show that such perfect dynamics necessitates the existence of atypical, nonergodic energy eigenstates - quantum many-body scars. Furthermore, using these insights, we construct a toy model that hosts exact quantum many-body scars, providing an intuitive explanation of their origin. Our results offer specific routes to enhancing coherent many-body revivals, and provide a step towards establishing the stability of quantum many-body scars in the thermodynamic limit.

Journal ArticleDOI
TL;DR: The Whole Atmosphere Community Climate Model version 6 (WACCM6) is a major update of the whole atmosphere modeling capability in the Community Earth System Model (CESM), featuring enhanced physical, chemical and aerosol parameterizations.
Abstract: The Whole Atmosphere Community Climate Model version 6 (WACCM6) is a major update of the whole atmosphere modeling capability in the Community Earth System Model (CESM), featuring enhanced physical, chemical and aerosol parameterizations. This work describes WACCM6 and some of the important features of the model. WACCM6 can reproduce many modes of variability and trends in the middle atmosphere, including the Quasi‐Biennial Oscillation, Stratospheric Sudden Warmings and the evolution of Southern Hemisphere springtime ozone depletion over the 20th century. WACCM6 can also reproduce the climate and temperature trends of the 20th century throughout the atmospheric column. The representation of the climate has improved in WACCM6, relative to WACCM4. In addition, there are improvements in high latitude climate variability at the surface and sea ice extent in WACCM6 over the lower top version of the model (CAM6) that come from the extended vertical domain and expanded aerosol chemistry in WACCM6, highlighting the importance of the stratosphere and tropospheric chemistry for high latitude climate variability.

Journal ArticleDOI
TL;DR: This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.
Abstract: Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody-drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.

Journal ArticleDOI
02 Sep 2019-Sensors
TL;DR: A review of near and remote sensor networks in the agriculture domain is presented along with several considerations and challenges and an IoT-based smart solution for crop health monitoring is proposed, which is comprised of two modules.
Abstract: Internet of Things (IoT)-based automation of agricultural events can change the agriculture sector from being static and manual to dynamic and smart, leading to enhanced production with reduced human efforts. Precision Agriculture (PA) along with Wireless Sensor Network (WSN) are the main drivers of automation in the agriculture domain. PA uses specific sensors and software to ensure that the crops receive exactly what they need to optimize productivity and sustainability. PA includes retrieving real data about the conditions of soil, crops and weather from the sensors deployed in the fields. High-resolution images of crops are obtained from satellite or air-borne platforms (manned or unmanned), which are further processed to extract information used to provide future decisions. In this paper, a review of near and remote sensor networks in the agriculture domain is presented along with several considerations and challenges. This survey includes wireless communication technologies, sensors, and wireless nodes used to assess the environmental behaviour, the platforms used to obtain spectral images of crops, the common vegetation indices used to analyse spectral images and applications of WSN in agriculture. As a proof of concept, we present a case study showing how WSN-based PA system can be implemented. We propose an IoT-based smart solution for crop health monitoring, which is comprised of two modules. The first module is a wireless sensor network-based system to monitor real-time crop health status. The second module uses a low altitude remote sensing platform to obtain multi-spectral imagery, which is further processed to classify healthy and unhealthy crops. We also highlight the results obtained using a case study and list the challenges and future directions based on our work.

Journal ArticleDOI
Floris P. Barthel1, Kevin C. Johnson, Frederick S. Varn, Anzhela D. Moskalik, Georgette Tanner2, Emre Kocakavuk3, Kevin J. Anderson, Olajide Abiola, Kenneth Aldape, Kristin Alfaro4, Donát Alpár5, Donát Alpár6, Samirkumar B. Amin, David M. Ashley7, Pratiti Bandopadhayay8, Pratiti Bandopadhayay9, Jill S. Barnholtz-Sloan10, Rameen Beroukhim8, Rameen Beroukhim9, Christoph Bock11, Christoph Bock5, Priscilla K. Brastianos9, Daniel J. Brat12, Andrew R Brodbelt13, Alexander F. Bruns2, Ketan R. Bulsara14, Aruna Chakrabarty15, Arnab Chakravarti16, Jeffrey H. Chuang14, Elizabeth B. Claus17, Elizabeth B. Claus18, Elizabeth J. Cochran19, Jennifer Connelly19, Joseph F. Costello20, Gaetano Finocchiaro, Michael N. C. Fletcher21, Pim J. French22, Hui K Gan23, Hui K Gan24, Mark R. Gilbert25, Peter Gould26, Matthew R. Grimmer20, Antonio Iavarone27, Azzam Ismail15, Michael D. Jenkinson13, Mustafa Khasraw28, Hoon Kim, Mathilde C.M. Kouwenhoven1, Peter S. LaViolette19, Meihong Li, Peter Lichter21, Keith L. Ligon9, Keith L. Ligon8, Allison Lowman19, Tathiane M. Malta29, Tali Mazor20, Kerrie L. McDonald30, Annette M. Molinaro20, Do-Hyun Nam31, Naema Nayyar9, Ho Keung Ng32, Chew Yee Ngan, Simone P. Niclou33, Johanna M. Niers1, Houtan Noushmehr29, Javad Noorbakhsh, D. Ryan Ormond34, Chul-Kee Park35, Laila M. Poisson29, Raul Rabadan36, Raul Rabadan27, Bernhard Radlwimmer21, Ganesh Rao4, Guido Reifenberger37, Jason K. Sa31, Michael Schuster5, Brian L. Shaw9, Susan C Short2, Peter A. E. Sillevis Smitt22, Andrew E. Sloan10, Andrew E. Sloan38, Marion Smits22, Hiromichi Suzuki39, Ghazaleh Tabatabai40, Erwin G. Van Meir41, Colin Watts42, Michael Weller43, Pieter Wesseling1, Bart A. Westerman1, Georg Widhalm11, Adelheid Woehrer11, W. K. Alfred Yung4, Gelareh Zadeh44, Jason T. Huse4, John de Groot4, Lucy F. Stead2, Roel G.W. Verhaak 
05 Dec 2019-Nature
TL;DR: The results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
Abstract: The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

Journal ArticleDOI
TL;DR: In this article, the authors show that through their consumption behavior, households are responsible for 72% of global greenhouse gas emissions and thus they are key actors in reaching the 1.5°C goal under the Paris Agreement.
Abstract: Through their consumption behavior, households are responsible for 72% of global greenhouse gas emissions. Thus, they are key actors in reaching the 1.5°C goal under the Paris Agreement. However, t ...

Journal ArticleDOI
Adriane Esquivel-Muelbert1, Timothy R. Baker1, Kyle G. Dexter2, Simon L. Lewis3, Simon L. Lewis1, Roel J. W. Brienen1, Ted R. Feldpausch4, Jon Lloyd5, Abel Monteagudo-Mendoza6, Luzmila Arroyo7, Esteban Álvarez-Dávila, Niro Higuchi8, Beatriz Schwantes Marimon9, Ben Hur Marimon-Junior9, Marcos Silveira10, Emilio Vilanova11, Emilio Vilanova12, Emanuel Gloor1, Yadvinder Malhi13, Jérôme Chave14, Jos Barlow15, Jos Barlow16, Damien Bonal17, Nallaret Davila Cardozo18, Terry L. Erwin19, Sophie Fauset1, Bruno Hérault20, Susan G. Laurance21, Lourens Poorter22, Lan Qie5, Clément Stahl23, Martin J. P. Sullivan1, Hans ter Steege24, Hans ter Steege25, Vincent A. Vos, Pieter A. Zuidema22, Everton Cristo de Almeida26, Edmar Almeida de Oliveira9, Ana Andrade8, Simone Aparecida Vieira27, Luiz E. O. C. Aragão4, Luiz E. O. C. Aragão28, Alejandro Araujo-Murakami7, Eric Arets22, Gerardo A. Aymard C, Christopher Baraloto29, Plínio Barbosa de Camargo30, Jorcely Barroso10, Frans Bongers22, René G. A. Boot31, José Luís Camargo8, Wendeson Castro10, Victor Chama Moscoso6, James A. Comiskey19, Fernando Cornejo Valverde32, Antonio Carlos Lola da Costa33, Jhon del Aguila Pasquel34, Jhon del Aguila Pasquel32, Anthony Di Fiore35, Luisa Fernanda Duque, Fernando Elias9, Julien Engel29, Julien Engel20, Gerardo Flores Llampazo, David W. Galbraith1, Rafael Herrera Fernández36, Rafael Herrera Fernández37, Eurídice N. Honorio Coronado34, Wannes Hubau38, Eliana Jimenez-Rojas39, Adriano José Nogueira Lima8, Ricardo Keichi Umetsu9, William F. Laurance21, Gabriela Lopez-Gonzalez1, Thomas E. Lovejoy40, Omar Aurelio Melo Cruz41, Paulo S. Morandi9, David A. Neill, Percy Núñez Vargas6, Nadir Pallqui Camacho6, Alexander Parada Gutierrez, Guido Pardo, Julie Peacock1, Marielos Peña-Claros22, Maria Cristina Peñuela-Mora, Pascal Petronelli14, Georgia Pickavance1, Nigel C. A. Pitman, Adriana Prieto42, Carlos A. Quesada8, Hirma Ramírez-Angulo11, Maxime Réjou-Méchain43, Zorayda Restrepo Correa, Anand Roopsind44, Agustín Rudas42, Rafael de Paiva Salomão15, Natalino Silva, Javier Silva Espejo45, James Singh46, Juliana Stropp47, John Terborgh48, Raquel Thomas44, Marisol Toledo7, Armando Torres-Lezama11, Luis Valenzuela Gamarra, Peter J. van de Meer49, Geertje M. F. van der Heijden50, Peter van der Hout, Rodolfo Vásquez Martínez, César I.A. Vela6, Ima Célia Guimarães Vieira15, Oliver L. Phillips1 
University of Leeds1, University of Edinburgh2, University College London3, University of Exeter4, Imperial College London5, National University of Saint Anthony the Abbot in Cuzco6, Universidad Autónoma Gabriel René Moreno7, National Institute of Amazonian Research8, Universidade do Estado de Mato Grosso9, Universidade Federal do Acre10, University of Los Andes11, University of Washington12, Environmental Change Institute13, Centre national de la recherche scientifique14, Museu Paraense Emílio Goeldi15, Lancaster University16, University of Lorraine17, Universidad Nacional de la Amazonía Peruana18, Smithsonian Institution19, University of Montpellier20, James Cook University21, Wageningen University and Research Centre22, Agro ParisTech23, Naturalis24, University of Amsterdam25, Federal University of Western Pará26, State University of Campinas27, National Institute for Space Research28, Florida International University29, University of São Paulo30, Tropenbos International31, Amazon.com32, Federal University of Pará33, Michigan Technological University34, University of Texas at Austin35, Venezuelan Institute for Scientific Research36, Polytechnic University of Valencia37, Royal Museum for Central Africa38, Tecnológico de Antioquia39, George Mason University40, Universidad del Tolima41, National University of Colombia42, Paul Sabatier University43, Georgetown University44, University of La Serena45, Forestry Commission46, Federal University of Alagoas47, Duke University48, Van Hall Larenstein University of Applied Sciences49, University of Nottingham50
TL;DR: A slow shift to a more dry‐affiliated Amazonia is underway, with changes in compositional dynamics consistent with climate‐change drivers, but yet to significantly impact whole‐community composition.
Abstract: Most of the planet's diversity is concentrated in the tropics, which includes many regions undergoing rapid climate change. Yet, while climate‐induced biodiversity changes are widely documented elsewhere, few studies have addressed this issue for lowland tropical ecosystems. Here we investigate whether the floristic and functional composition of intact lowland Amazonian forests have been changing by evaluating records from 106 long‐term inventory plots spanning 30 years. We analyse three traits that have been hypothesized to respond to different environmental drivers (increase in moisture stress and atmospheric CO2 concentrations): maximum tree size, biogeographic water‐deficit affiliation and wood density. Tree communities have become increasingly dominated by large‐statured taxa, but to date there has been no detectable change in mean wood density or water deficit affiliation at the community level, despite most forest plots having experienced an intensification of the dry season. However, among newly recruited trees, dry‐affiliated genera have become more abundant, while the mortality of wet‐affiliated genera has increased in those plots where the dry season has intensified most. Thus, a slow shift to a more dry‐affiliated Amazonia is underway, with changes in compositional dynamics (recruits and mortality) consistent with climate‐change drivers, but yet to significantly impact whole‐community composition. The Amazon observational record suggests that the increase in atmospheric CO2 is driving a shift within tree communities to large‐statured species and that climate changes to date will impact forest composition, but long generation times of tropical trees mean that biodiversity change is lagging behind climate change.

Journal ArticleDOI
19 Sep 2019-Nature
TL;DR: It is shown that more realistic modelling scenarios do not produce a substantial near-term increase in either the magnitude or the rate of warming, and in fact can lead to a decrease in warming rates within two decades of the start of the fossil-fuel phase-out.
Abstract: The combustion of fossil fuels produces emissions of the long-lived greenhouse gas carbon dioxide and of short-lived pollutants, including sulfur dioxide, that contribute to the formation of atmospheric aerosols1. Atmospheric aerosols can cool the climate, masking some of the warming effect that results from the emission of greenhouse gases1. However, aerosol particulates are highly toxic when inhaled, leading to millions of premature deaths per year2,3. The phasing out of unabated fossil-fuel combustion will therefore provide health benefits, but will also reduce the extent to which the warming induced by greenhouse gases is masked by aerosols. Because aerosol levels respond much more rapidly to changes in emissions relative to carbon dioxide, large near-term increases in the magnitude and rate of climate warming are predicted in many idealized studies that typically assume an instantaneous removal of all anthropogenic or fossil-fuel-related emissions1,4-9. Here we show that more realistic modelling scenarios do not produce a substantial near-term increase in either the magnitude or the rate of warming, and in fact can lead to a decrease in warming rates within two decades of the start of the fossil-fuel phase-out. Accounting for the time required to transform power generation, industry and transportation leads to gradually increasing and largely offsetting climate impacts of carbon dioxide and sulfur dioxide, with the rate of warming further slowed by reductions in fossil-methane emissions. Our results indicate that even the most aggressive plausible transition to a clean-energy society provides benefits for climate change mitigation and air quality at essentially all decadal to centennial timescales.

Journal ArticleDOI
TL;DR: A meta-analysis focussing on birds suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits and indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
Abstract: Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.