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Showing papers by "Lund University published in 2019"


Journal ArticleDOI
TL;DR: This work presents the results of a meta-analysis conducted at the 2016 European Oncology and Radiotherapy Guidelines Working Group (ESMO) workshop on breast cancer diagnosis and prognosis of women with atypical central giant cell granuloma (CGM) who have previously had surgery.

2,274 citations


Journal ArticleDOI
TL;DR: The multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress are described.
Abstract: Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.

1,708 citations



Journal ArticleDOI
TL;DR: In this article, the authors provide an extensive review and an updated research agenda for the field, classified into nine main themes: understanding transitions; power, agency and politics; governing transitions; civil society, culture and social movements; businesses and industries; transitions in practice and everyday life; geography of transitions; ethical aspects; and methodologies.
Abstract: Research on sustainability transitions has expanded rapidly in the last ten years, diversified in terms of topics and geographical applications, and deepened with respect to theories and methods. This article provides an extensive review and an updated research agenda for the field, classified into nine main themes: understanding transitions; power, agency and politics; governing transitions; civil society, culture and social movements; businesses and industries; transitions in practice and everyday life; geography of transitions; ethical aspects; and methodologies. The review shows that the scope of sustainability transitions research has broadened and connections to established disciplines have grown stronger. At the same time, we see that the grand challenges related to sustainability remain unsolved, calling for continued efforts and an acceleration of ongoing transitions. Transition studies can play a key role in this regard by creating new perspectives, approaches and understanding and helping to move society in the direction of sustainability.

1,099 citations


Journal ArticleDOI
Pierre Friedlingstein1, Pierre Friedlingstein2, Matthew W. Jones3, Michael O'Sullivan2, Robbie M. Andrew, Judith Hauck4, Glen P. Peters, Wouter Peters5, Wouter Peters6, Julia Pongratz7, Julia Pongratz8, Stephen Sitch2, Corinne Le Quéré3, Dorothee C. E. Bakker3, Josep G. Canadell9, Philippe Ciais10, Robert B. Jackson11, Peter Anthoni12, Leticia Barbero13, Leticia Barbero14, Ana Bastos7, Vladislav Bastrikov10, Meike Becker15, Meike Becker16, Laurent Bopp1, Erik T. Buitenhuis3, Naveen Chandra17, Frédéric Chevallier10, Louise Chini18, Kim I. Currie19, Richard A. Feely20, Marion Gehlen10, Dennis Gilfillan21, Thanos Gkritzalis22, Daniel S. Goll23, Nicolas Gruber24, Sören B. Gutekunst25, Ian Harris26, Vanessa Haverd9, Richard A. Houghton27, George C. Hurtt18, Tatiana Ilyina8, Atul K. Jain28, Emilie Joetzjer10, Jed O. Kaplan29, Etsushi Kato, Kees Klein Goldewijk30, Kees Klein Goldewijk31, Jan Ivar Korsbakken, Peter Landschützer8, Siv K. Lauvset15, Nathalie Lefèvre32, Andrew Lenton33, Andrew Lenton34, Sebastian Lienert35, Danica Lombardozzi36, Gregg Marland21, Patrick C. McGuire37, Joe R. Melton, Nicolas Metzl32, David R. Munro38, Julia E. M. S. Nabel8, Shin-Ichiro Nakaoka39, Craig Neill34, Abdirahman M Omar15, Abdirahman M Omar34, Tsuneo Ono, Anna Peregon10, Anna Peregon40, Denis Pierrot13, Denis Pierrot14, Benjamin Poulter41, Gregor Rehder42, Laure Resplandy43, Eddy Robertson44, Christian Rödenbeck8, Roland Séférian10, Jörg Schwinger30, Jörg Schwinger15, Naomi E. Smith5, Naomi E. Smith45, Pieter P. Tans20, Hanqin Tian46, Bronte Tilbrook33, Bronte Tilbrook34, Francesco N. Tubiello47, Guido R. van der Werf48, Andy Wiltshire44, Sönke Zaehle8 
École Normale Supérieure1, University of Exeter2, Norwich Research Park3, Alfred Wegener Institute for Polar and Marine Research4, Wageningen University and Research Centre5, University of Groningen6, Ludwig Maximilian University of Munich7, Max Planck Society8, Commonwealth Scientific and Industrial Research Organisation9, Centre national de la recherche scientifique10, Stanford University11, Karlsruhe Institute of Technology12, Cooperative Institute for Marine and Atmospheric Studies13, Atlantic Oceanographic and Meteorological Laboratory14, Bjerknes Centre for Climate Research15, Geophysical Institute, University of Bergen16, Japan Agency for Marine-Earth Science and Technology17, University of Maryland, College Park18, National Institute of Water and Atmospheric Research19, National Oceanic and Atmospheric Administration20, Appalachian State University21, Flanders Marine Institute22, Augsburg College23, ETH Zurich24, Leibniz Institute of Marine Sciences25, University of East Anglia26, Woods Hole Research Center27, University of Illinois at Urbana–Champaign28, University of Hong Kong29, Netherlands Environmental Assessment Agency30, Utrecht University31, University of Paris32, University of Tasmania33, Hobart Corporation34, University of Bern35, National Center for Atmospheric Research36, University of Reading37, Cooperative Institute for Research in Environmental Sciences38, National Institute for Environmental Studies39, Russian Academy of Sciences40, Goddard Space Flight Center41, Leibniz Institute for Baltic Sea Research42, Princeton University43, Met Office44, Lund University45, Auburn University46, Food and Agriculture Organization47, VU University Amsterdam48
TL;DR: In this article, the authors describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties, including emissions from land use and land use change, and show that the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere is a measure of imperfect data and understanding of the contemporary carbon cycle.
Abstract: . Accurate assessment of anthropogenic carbon dioxide ( CO2 ) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions ( EFF ) are based on energy statistics and cement production data, while emissions from land use change ( ELUC ), mainly deforestation, are based on land use and land use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly and its growth rate ( GATM ) is computed from the annual changes in concentration. The ocean CO2 sink ( SOCEAN ) and terrestrial CO2 sink ( SLAND ) are estimated with global process models constrained by observations. The resulting carbon budget imbalance ( BIM ), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ . For the last decade available (2009–2018), EFF was 9.5±0.5 GtC yr −1 , ELUC 1.5±0.7 GtC yr −1 , GATM 4.9±0.02 GtC yr −1 ( 2.3±0.01 ppm yr −1 ), SOCEAN 2.5±0.6 GtC yr −1 , and SLAND 3.2±0.6 GtC yr −1 , with a budget imbalance BIM of 0.4 GtC yr −1 indicating overestimated emissions and/or underestimated sinks. For the year 2018 alone, the growth in EFF was about 2.1 % and fossil emissions increased to 10.0±0.5 GtC yr −1 , reaching 10 GtC yr −1 for the first time in history, ELUC was 1.5±0.7 GtC yr −1 , for total anthropogenic CO2 emissions of 11.5±0.9 GtC yr −1 ( 42.5±3.3 GtCO2 ). Also for 2018, GATM was 5.1±0.2 GtC yr −1 ( 2.4±0.1 ppm yr −1 ), SOCEAN was 2.6±0.6 GtC yr −1 , and SLAND was 3.5±0.7 GtC yr −1 , with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 407.38±0.1 ppm averaged over 2018. For 2019, preliminary data for the first 6–10 months indicate a reduced growth in EFF of +0.6 % (range of −0.2 % to 1.5 %) based on national emissions projections for China, the USA, the EU, and India and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. Overall, the mean and trend in the five components of the global carbon budget are consistently estimated over the period 1959–2018, but discrepancies of up to 1 GtC yr −1 persist for the representation of semi-decadal variability in CO2 fluxes. A detailed comparison among individual estimates and the introduction of a broad range of observations shows (1) no consensus in the mean and trend in land use change emissions over the last decade, (2) a persistent low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) an apparent underestimation of the CO2 variability by ocean models outside the tropics. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Le Quere et al., 2018a, b, 2016, 2015a, b, 2014, 2013). The data generated by this work are available at https://doi.org/10.18160/gcp-2019 (Friedlingstein et al., 2019).

981 citations


Journal ArticleDOI
TL;DR: Climate change strongly impacts regions in high latitudes and altitudes that store high amounts of carbon in yet frozen ground, and the authors show that the consequence of these changes is global warming of permafrost at depths greater than 10 m in the Northern Hemisphere, in mountains, and in Antarctica.
Abstract: Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007–2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.

906 citations


Journal ArticleDOI
TL;DR: Overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups.
Abstract: Background Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. Methods In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. Results A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P Conclusions In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).

789 citations


Journal ArticleDOI
Andrea Cossarizza1, Hyun-Dong Chang, Andreas Radbruch, Andreas Acs2  +459 moreInstitutions (160)
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

698 citations


Journal ArticleDOI
Nasim Mavaddat1, Kyriaki Michailidou1, Kyriaki Michailidou2, Joe Dennis1  +307 moreInstitutions (105)
TL;DR: This PRS, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset is developed and empirically validated and is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

653 citations


Journal ArticleDOI
TL;DR: A meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer identified a core set of 29 species significantly enriched in CRC metagenomes, establishing globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
Abstract: Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10−5). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics. Cross-study analysis defines fecal microbial species associated with colorectal cancer.

615 citations


Journal ArticleDOI
TL;DR: High-definition spatial transcriptomics is developed, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array, which opens the way to high-resolution spatial analysis of cells and tissues.
Abstract: Spatial and molecular characteristics determine tissue function, yet high-resolution methods to capture both concurrently are lacking. Here, we developed high-definition spatial transcriptomics, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array. Each experiment recovers several hundred thousand transcript-coupled spatial barcodes at 2-μm resolution, as demonstrated in mouse brain and primary breast cancer. This opens the way to high-resolution spatial analysis of cells and tissues.

Journal ArticleDOI
TL;DR: The OpenMolcas environment is described and features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism and properties are described.
Abstract: In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.

Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1491 moreInstitutions (239)
TL;DR: In this article, the authors present the second volume of the Future Circular Collider Conceptual Design Report, devoted to the electron-positron collider FCC-ee, and present the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan.
Abstract: In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

Journal ArticleDOI
TL;DR: In this paper, the authors conduct a morphological analysis of 26 current circular economy business models from the literature, which includes defining their major business model dimensions and identifying the specific characteristics of these dimensions.
Abstract: The circular economy (CE) requires companies to rethink their supply chains and business models. Several frameworks found in the academic and practitioner literature propose circular economy business models (CEBMs) to redefine how companies create value while adhering to CE principles. A review of these frameworks shows that some models are frequently discussed, some are framework specific, and some use a different wording to refer to similar CEBMs, pointing to the need to consolidate the current state of the art. We conduct a morphological analysis of 26 current CEBMs from the literature, which includes defining their major business model dimensions and identifying the specific characteristics of these dimensions. Based on this analysis, we identify a broad range of business model design options and propose six major CEBM patterns with the potential to support the closing of resource flows: repair and maintenance; reuse and redistribution; refurbishment and remanufacturing; recycling; cascading and repurposing; and organic feedstock business model patterns. We also discuss different design strategies to support the development of these CEBMs. (Less)

Journal ArticleDOI
Heather Orpana1, Heather Orpana2, Laurie B. Marczak3, Megha Arora3  +338 moreInstitutions (173)
06 Feb 2019-BMJ
TL;DR: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide and can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Abstract: Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

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.

Journal ArticleDOI
TL;DR: There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy, consistent with the physician-evaluated toxicity.

Journal ArticleDOI
TL;DR: This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism—i.e., adipose tissue, skeletal muscle, pancreatic islets, liver, and blood—in relation to obesity and T2D to support not only a role for epigenetics in disease development, but also epigenetic alterations as a response to disease.

Journal ArticleDOI
TL;DR: In this article, key observational indicators of climate change in the Arctic, most spanning a 47-year period (1971-2017) demonstrate fundamental changes among nine key elements of the Arctic system.
Abstract: Key observational indicators of climate change in the Arctic, most spanning a 47 year period (1971–2017) demonstrate fundamental changes among nine key elements of the Arctic system. We find that, coherent with increasing air temperature, there is an intensification of the hydrological cycle, evident from increases in humidity, precipitation, river discharge, glacier equilibrium line altitude and land ice wastage. Downward trends continue in sea ice thickness (and extent) and spring snow cover extent and duration, while near-surface permafrost continues to warm. Several of the climate indicators exhibit a significant statistical correlation with air temperature or precipitation, reinforcing the notion that increasing air temperatures and precipitation are drivers of major changes in various components of the Arctic system. To progress beyond a presentation of the Arctic physical climate changes, we find a correspondence between air temperature and biophysical indicators such as tundra biomass and identify numerous biophysical disruptions with cascading effects throughout the trophic levels. These include: increased delivery of organic matter and nutrients to Arctic near‐coastal zones; condensed flowering and pollination plant species periods; timing mismatch between plant flowering and pollinators; increased plant vulnerability to insect disturbance; increased shrub biomass; increased ignition of wildfires; increased growing season CO2 uptake, with counterbalancing increases in shoulder season and winter CO2 emissions; increased carbon cycling, regulated by local hydrology and permafrost thaw; conversion between terrestrial and aquatic ecosystems; and shifting animal distribution and demographics. The Arctic biophysical system is now clearly trending away from its 20th Century state and into an unprecedented state, with implications not only within but beyond the Arctic. The indicator time series of this study are freely downloadable at AMAP.no.

Journal ArticleDOI
Matteo Dainese1, Emily A. Martin1, Marcelo A. Aizen2, Matthias Albrecht, Ignasi Bartomeus3, Riccardo Bommarco4, Luísa G. Carvalheiro5, Luísa G. Carvalheiro6, Rebecca Chaplin-Kramer7, Vesna Gagic8, Lucas Alejandro Garibaldi9, Jaboury Ghazoul10, Heather Grab11, Mattias Jonsson4, Daniel S. Karp12, Christina M. Kennedy13, David Kleijn14, Claire Kremen15, Douglas A. Landis16, Deborah K. Letourneau17, Lorenzo Marini18, Katja Poveda11, Romina Rader19, Henrik G. Smith20, Teja Tscharntke21, Georg K.S. Andersson20, Isabelle Badenhausser22, Isabelle Badenhausser23, Svenja Baensch21, Antonio Diego M. Bezerra24, Felix J.J.A. Bianchi14, Virginie Boreux25, Virginie Boreux10, Vincent Bretagnolle22, Berta Caballero-López, Pablo Cavigliasso26, Aleksandar Ćetković27, Natacha P. Chacoff28, Alice Classen1, Sarah Cusser29, Felipe D. da Silva e Silva30, G. Arjen de Groot14, Jan H. Dudenhöffer31, Johan Ekroos20, Thijs P.M. Fijen14, Pierre Franck23, Breno Magalhães Freitas24, Michael P.D. Garratt32, Claudio Gratton33, Juliana Hipólito9, Juliana Hipólito34, Andrea Holzschuh1, Lauren Hunt35, Aaron L. Iverson11, Shalene Jha36, Tamar Keasar37, Tania N. Kim38, Miriam Kishinevsky37, Björn K. Klatt21, Björn K. Klatt20, Alexandra-Maria Klein25, Kristin M. Krewenka39, Smitha Krishnan10, Smitha Krishnan40, Ashley E. Larsen41, Claire Lavigne23, Heidi Liere42, Bea Maas43, Rachel E. Mallinger44, Eliana Martinez Pachon, Alejandra Martínez-Salinas45, Timothy D. Meehan46, Matthew G. E. Mitchell15, Gonzalo Alberto Roman Molina47, Maike Nesper10, Lovisa Nilsson20, Megan E. O'Rourke48, Marcell K. Peters1, Milan Plećaš27, Simon G. Potts33, Davi de L. Ramos, Jay A. Rosenheim12, Maj Rundlöf20, Adrien Rusch49, Agustín Sáez2, Jeroen Scheper14, Matthias Schleuning, Julia Schmack50, Amber R. Sciligo51, Colleen L. Seymour, Dara A. Stanley52, Rebecca Stewart20, Jane C. Stout53, Louis Sutter, Mayura B. Takada54, Hisatomo Taki, Giovanni Tamburini25, Matthias Tschumi, Blandina Felipe Viana55, Catrin Westphal21, Bryony K. Willcox19, Stephen D. Wratten56, Akira Yoshioka57, Carlos Zaragoza-Trello3, Wei Zhang58, Yi Zou59, Ingolf Steffan-Dewenter1 
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, Universidade Federal de Goiás5, University of Lisbon6, Stanford University7, Commonwealth Scientific and Industrial Research Organisation8, National University of Río Negro9, ETH Zurich10, Cornell University11, University of California, Davis12, The Nature Conservancy13, Wageningen University and Research Centre14, University of British Columbia15, Great Lakes Bioenergy Research Center16, University of California, Santa Cruz17, University of Padua18, University of New England (Australia)19, Lund University20, University of Göttingen21, University of La Rochelle22, Institut national de la recherche agronomique23, Federal University of Ceará24, University of Freiburg25, Concordia University Wisconsin26, University of Belgrade27, National University of Tucumán28, Michigan State University29, University of Brasília30, University of Greenwich31, University of Reading32, University of Wisconsin-Madison33, National Institute of Amazonian Research34, Boise State University35, University of Texas at Austin36, University of Haifa37, Kansas State University38, University of Hamburg39, Bioversity International40, University of California, Santa Barbara41, Seattle University42, University of Vienna43, University of Florida44, Centro Agronómico Tropical de Investigación y Enseñanza45, National Audubon Society46, University of Buenos Aires47, Virginia Tech48, University of Bordeaux49, University of Auckland50, University of California, Berkeley51, University College Dublin52, Trinity College, Dublin53, University of Tokyo54, Federal University of Bahia55, Lincoln University (New Zealand)56, National Institute for Environmental Studies57, International Food Policy Research Institute58, Xi'an Jiaotong-Liverpool University59
TL;DR: Using a global database from 89 studies (with 1475 locations), the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change is partitioned.
Abstract: Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

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A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1496 moreInstitutions (238)
TL;DR: In this paper, the authors describe the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider in collaboration with national institutes, laboratories and universities worldwide, and enhanced by a strong participation of industrial partners.
Abstract: Particle physics has arrived at an important moment of its history. The discovery of the Higgs boson, with a mass of 125 GeV, completes the matrix of particles and interactions that has constituted the “Standard Model” for several decades. This model is a consistent and predictive theory, which has so far proven successful at describing all phenomena accessible to collider experiments. However, several experimental facts do require the extension of the Standard Model and explanations are needed for observations such as the abundance of matter over antimatter, the striking evidence for dark matter and the non-zero neutrino masses. Theoretical issues such as the hierarchy problem, and, more in general, the dynamical origin of the Higgs mechanism, do likewise point to the existence of physics beyond the Standard Model. This report contains the description of a novel research infrastructure based on a highest-energy hadron collider with a centre-of-mass collision energy of 100 TeV and an integrated luminosity of at least a factor of 5 larger than the HL-LHC. It will extend the current energy frontier by almost an order of magnitude. The mass reach for direct discovery will reach several tens of TeV, and allow, for example, to produce new particles whose existence could be indirectly exposed by precision measurements during the earlier preceding e+e– collider phase. This collider will also precisely measure the Higgs self-coupling and thoroughly explore the dynamics of electroweak symmetry breaking at the TeV scale, to elucidate the nature of the electroweak phase transition. WIMPs as thermal dark matter candidates will be discovered, or ruled out. As a single project, this particle collider infrastructure will serve the world-wide physics community for about 25 years and, in combination with a lepton collider (see FCC conceptual design report volume 2), will provide a research tool until the end of the 21st century. Collision energies beyond 100 TeV can be considered when using high-temperature superconductors. The European Strategy for Particle Physics (ESPP) update 2013 stated “To stay at the forefront of particle physics, Europe needs to be in a position to propose an ambitious post-LHC accelerator project at CERN by the time of the next Strategy update”. The FCC study has implemented the ESPP recommendation by developing a long-term vision for an “accelerator project in a global context”. This document describes the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider “in collaboration with national institutes, laboratories and universities worldwide”, and enhanced by a strong participation of industrial partners. Now, a coordinated preparation effort can be based on a core of an ever-growing consortium of already more than 135 institutes worldwide. The technology for constructing a high-energy circular hadron collider can be brought to the technology readiness level required for constructing within the coming ten years through a focused R&D programme. The FCC-hh concept comprises in the baseline scenario a power-saving, low-temperature superconducting magnet system based on an evolution of the Nb3Sn technology pioneered at the HL-LHC, an energy-efficient cryogenic refrigeration infrastructure based on a neon-helium (Nelium) light gas mixture, a high-reliability and low loss cryogen distribution infrastructure based on Invar, high-power distributed beam transfer using superconducting elements and local magnet energy recovery and re-use technologies that are already gradually introduced at other CERN accelerators. On a longer timescale, high-temperature superconductors can be developed together with industrial partners to achieve an even more energy efficient particle collider or to reach even higher collision energies.The re-use of the LHC and its injector chain, which also serve for a concurrently running physics programme, is an essential lever to come to an overall sustainable research infrastructure at the energy frontier. Strategic R&D for FCC-hh aims at minimising construction cost and energy consumption, while maximising the socio-economic impact. It will mitigate technology-related risks and ensure that industry can benefit from an acceptable utility. Concerning the implementation, a preparatory phase of about eight years is both necessary and adequate to establish the project governance and organisation structures, to build the international machine and experiment consortia, to develop a territorial implantation plan in agreement with the host-states’ requirements, to optimise the disposal of land and underground volumes, and to prepare the civil engineering project. Such a large-scale, international fundamental research infrastructure, tightly involving industrial partners and providing training at all education levels, will be a strong motor of economic and societal development in all participating nations. The FCC study has implemented a set of actions towards a coherent vision for the world-wide high-energy and particle physics community, providing a collaborative framework for topically complementary and geographically well-balanced contributions. This conceptual design report lays the foundation for a subsequent infrastructure preparatory and technical design phase.

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Claire Bridel1, van Wieringen Wn1, Henrik Zetterberg2, Betty M. Tijms1, Charlotte E. Teunissen1, José C. Álvarez-Cermeño, Ulf Andreasson2, Markus Axelsson3, David Bäckström4, Ales Bartos5, Maria Bjerke6, Kaj Blennow3, Kaj Blennow2, A. Boxer7, Lena Brundin8, Joachim Burman9, Tove Christensen10, Lenka Fialová11, Lars Forsgren4, Jette L. Frederiksen12, Magnus Gisslén3, Elizabeth Gray13, Martin Gunnarsson14, Sara Hall15, Oskar Hansson15, Megan K. Herbert3, Joel Jakobsson3, Jessen-Krut J3, Shorena Janelidze15, Gudmundur Johannsson2, Gudmundur Johannsson3, Michael Jonsson3, Ludwig Kappos16, Mohsen Khademi17, Mohsen Khademi8, Michael Khalil18, Jens Kuhle16, Mikael Landén3, Leinonen19, Giancarlo Logroscino20, Lu Ch, Jan Lycke3, Nadia K. Magdalinou21, Andrea Malaspina, Niklas Mattsson15, Lieke H.H. Meeter22, Mehta23, Signe Modvig12, Tomas Olsson8, Tomas Olsson17, Ross W. Paterson21, Pérez-Santiago J24, Fredrik Piehl17, Fredrik Piehl8, Pijnenburg Yal1, Pyykkö Ot19, Ragnarsson O14, Julio C. Rojas7, Romme Christensen J12, Sandberg L4, Carole Scherling25, Jonathan M. Schott21, Finn Sellebjerg12, Isabella Laura Simone20, Tobias Skillbäck3, Stilund M10, Peter Sundström4, Anders Svenningsson8, Rosanna Tortelli20, Carla Tortorella20, Alessandro Trentini26, Troiano M20, Martin R Turner13, van Swieten Jc22, Mattias Vågberg4, Marcel M. Verbeek27, Luisa M. Villar, Pieter Jelle Visser1, Pieter Jelle Visser28, Anders Wallin3, Weiss A29, Carsten Wikkelsö3, Edward J. Wild21 
TL;DR: The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC, and has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
Abstract: Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses. Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

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TL;DR: The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
Abstract: Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

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TL;DR: This Review defines HOM and describes the currently available techniques for their identification/quantification, followed by a summary of the current knowledge on their formation mechanisms and physicochemical properties.
Abstract: Highly oxygenated organic molecules (HOM) are formed in the atmosphere via autoxidation involving peroxy radicals arising from volatile organic compounds (VOC). HOM condense on pre-existing particles and can be involved in new particle formation. HOM thus contribute to the formation of secondary organic aerosol (SOA), a significant and ubiquitous component of atmospheric aerosol known to affect the Earth's radiation balance. HOM were discovered only very recently, but the interest in these compounds has grown rapidly. In this Review, we define HOM and describe the currently available techniques for their identification/quantification, followed by a summary of the current knowledge on their formation mechanisms and physicochemical properties. A main aim is to provide a common frame for the currently quite fragmented literature on HOM studies. Finally, we highlight the existing gaps in our understanding and suggest directions for future HOM research.

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A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1501 moreInstitutions (239)
TL;DR: In this article, the physics opportunities of the Future Circular Collider (FC) were reviewed, covering its e+e-, pp, ep and heavy ion programs, and the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions.
Abstract: We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics.

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TL;DR: In this article, a comprehensive overview of ecosystem services provided by natural and semi-natural grasslands, using southern Africa (SA) and northwest Europe as case studies, respectively, is presented.
Abstract: Extensively managed grasslands are recognized globally for their high biodiversity and their social and cultural values. However, their capacity to deliver multiple ecosystem services (ES) as parts of agricultural systems is surprisingly understudied compared to other production systems. We undertook a comprehensive overview of ES provided by natural and semi-natural grasslands, using southern Africa (SA) and northwest Europe as case studies, respectively. We show that these grasslands can supply additional non-agricultural services, such as water supply and flow regulation, carbon storage, erosion control, climate mitigation, pollination, and cultural ES. While demand for ecosystems services seems to balance supply in natural grasslands of SA, the smaller areas of semi-natural grasslands in Europe appear to not meet the demand for many services. We identified three bundles of related ES from grasslands: water ES including fodder production, cultural ES connected to livestock production, and population-based regulating services (e.g., pollination and biological control), which also linked to biodiversity. Greenhouse gas emission mitigation seemed unrelated to the three bundles. The similarities among the bundles in SA and northwestern Europe suggest that there are generalities in ES relations among natural and semi-natural grassland areas. We assessed trade-offs and synergies among services in relation to management practices and found that although some trade-offs are inevitable, appropriate management may create synergies and avoid trade-offs among many services. We argue that ecosystem service and food security research and policy should give higher priority to how grasslands can be managed for fodder and meat production alongside other ES. By integrating grasslands into agricultural production systems and land-use decisions locally and regionally, their potential to contribute to functional landscapes and to food security and sustainable livelihoods can be greatly enhanced. (Less)

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TL;DR: The findings suggest that plasma NfL can be used as a noninvasive biomarker associated with neurodegeneration in patients with AD and may be useful to monitor effects in trials of disease-modifying drugs.
Abstract: Importance Plasma neurofilament light (NfL) has been suggested as a noninvasive biomarker to monitor neurodegeneration in Alzheimer disease (AD), but studies are lacking. Objective To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD. Design, Setting, and Participants This North American cohort study used data from 1583 individuals in the multicenter Alzheimer’s Disease Neuroimaging Initiative study from September 7, 2005, through June 16, 2016. Patients were eligible for inclusion if they had NfL measurements. Annual plasma NfL samples were collected for up to 11 years and were analyzed in 2018. Exposures Clinical diagnosis, Aβ and tau cerebrospinal fluid (CSF) biomarkers, imaging measures (magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography), and tests on cognitive scores. Main Outcomes and Measures The primary outcome was the association between baseline exposures (diagnosis, CSF biomarkers, imaging measures, and cognition) and longitudinal plasma NfL levels, analyzed by an ultrasensitive assay. The secondary outcomes were the associations between a multimodal classification scheme with Aβ, tau, and neurodegeneration (ie, the ATN system) and plasma NfL levels and between longitudinal changes in plasma NfL levels and changes in the other measures. Results Of the included 1583 participants, 716 (45.2%) were women, and the mean (SD) age was 72.9 (7.1) years; 401 had no cognitive impairment, 855 had mild cognitive impairment, and 327 had AD dementia. The NfL level was increased at baseline in patients with mild cognitive impairment and AD dementia (mean levels: cognitive unimpairment, 32.1 ng/L; mild cognitive impairment, 37.9 ng/L; and AD dementia, 45.9 ng/L;P Conclusions and Relevance The findings suggest that plasma NfL can be used as a noninvasive biomarker associated with neurodegeneration in patients with AD and may be useful to monitor effects in trials of disease-modifying drugs.

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TL;DR: The results suggest OPVs have the potential for further improvement by judicious modulation of ESP and the theoretical studies reveal that the molecular electrostatic potential between PTO2 and IT-4F is large, and the induced intermolecular electric field may assist the charge generation.
Abstract: Although significant improvements have been achieved for organic photovoltaic cells (OPVs), the top-performing devices still show power conversion efficiencies far behind those of commercialized solar cells. One of the main reasons is the large driving force required for separating electron-hole pairs. Here, we demonstrate an efficiency of 14.7% in the single-junction OPV by using a new polymer donor PTO2 and a nonfullerene acceptor IT-4F. The device possesses an efficient charge generation at a low driving force. Ultrafast transient absorption measurements probe the formation of loosely bound charge pairs with extended lifetime that impedes the recombination of charge carriers in the blend. The theoretical studies reveal that the molecular electrostatic potential (ESP) between PTO2 and IT-4F is large, and the induced intermolecular electric field may assist the charge generation. The results suggest OPVs have the potential for further improvement by judicious modulation of ESP.

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TL;DR: In this paper, the authors derived short distance constraints for the hadronic light-by-light contribution (HLbL) to the anomalous magnetic moment of the muon in the kinematic region where the three virtual momenta are all large.

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TL;DR: A systematic review of chronic wounds revealed that health‐related quality of life was lowest for physical pathologies, and based on average estimates were scores most inferior in the domain physical role for both patients with chronic wounds and for those with wound‐related amputations.
Abstract: Chronic wounds are a health problem that have devastating consequences for patients and contribute major costs to healthcare systems and societies. To understand the magnitude of this health issue, a systematic review was undertaken. Searches were conducted in MEDLINE, EMBASE, EBM Reviews and Cochrane library, CINAHL, EBSCO, PsycINFO, and Global Health databases for articles published between 2000 and 2015. Included publications had to target adults (≥18 years of age), state wound chronicity (≥3 weeks) and/or label the wounds as chronic, complex, hard-to-heal, or having led to an amputation. The review excluded studies that did not present data on generic health-related quality of life and/or cost data, case studies, randomized controlled trials, economic modeling studies, abstracts, and editorials. Extracted data were summarized into a narrative synthesis, and for a few articles using the same health-related quality of life instrument, average estimates with 95% confidence intervals were calculated. Thirty articles met the inclusion criteria. Findings revealed that health-related quality of life was lowest for physical pathologies, and based on average estimates were scores most inferior in the domain physical role for both patients with chronic wounds and for those with wound-related amputations. The cost burden was mainly attributed to amputations for patients also comorbid with diabetes, where the cost for hospitalization ranged from US$12,851 to US$16,267 (median) for this patient group. Patients with chronic wounds have poor health-related quality of life in general and wound-related costs are substantial. Development and implementation of wound management strategies that focus on increasing health-related quality of life and effectively reduce costs for this patient group are urgently needed.