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Showing papers by "University of Erlangen-Nuremberg published in 2019"


Journal ArticleDOI
TL;DR: An emphasis is placed on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarc Openia diagnosis, and provides clear cut-off points for measurements of variables that identify and characterise sarc openia.
Abstract: Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

6,250 citations


Journal ArticleDOI
Frank Arute1, Kunal Arya1, Ryan Babbush1, Dave Bacon1, Joseph C. Bardin1, Joseph C. Bardin2, Rami Barends1, Rupak Biswas3, Sergio Boixo1, Fernando G. S. L. Brandão1, Fernando G. S. L. Brandão4, David A. Buell1, B. Burkett1, Yu Chen1, Zijun Chen1, Ben Chiaro5, Roberto Collins1, William Courtney1, Andrew Dunsworth1, Edward Farhi1, Brooks Foxen1, Brooks Foxen5, Austin G. Fowler1, Craig Gidney1, Marissa Giustina1, R. Graff1, Keith Guerin1, Steve Habegger1, Matthew P. Harrigan1, Michael J. Hartmann6, Michael J. Hartmann1, Alan Ho1, Markus R. Hoffmann1, Trent Huang1, Travis S. Humble7, Sergei V. Isakov1, Evan Jeffrey1, Zhang Jiang1, Dvir Kafri1, Kostyantyn Kechedzhi1, Julian Kelly1, Paul V. Klimov1, Sergey Knysh1, Alexander N. Korotkov1, Alexander N. Korotkov8, Fedor Kostritsa1, David Landhuis1, Mike Lindmark1, E. Lucero1, Dmitry I. Lyakh7, Salvatore Mandrà3, Jarrod R. McClean1, Matt McEwen5, Anthony Megrant1, Xiao Mi1, Kristel Michielsen9, Kristel Michielsen10, Masoud Mohseni1, Josh Mutus1, Ofer Naaman1, Matthew Neeley1, Charles Neill1, Murphy Yuezhen Niu1, Eric Ostby1, Andre Petukhov1, John Platt1, Chris Quintana1, Eleanor Rieffel3, Pedram Roushan1, Nicholas C. Rubin1, Daniel Sank1, Kevin J. Satzinger1, Vadim Smelyanskiy1, Kevin J. Sung1, Kevin J. Sung11, Matthew D. Trevithick1, Amit Vainsencher1, Benjamin Villalonga12, Benjamin Villalonga1, Theodore White1, Z. Jamie Yao1, Ping Yeh1, Adam Zalcman1, Hartmut Neven1, John M. Martinis1, John M. Martinis5 
24 Oct 2019-Nature
TL;DR: Quantum supremacy is demonstrated using a programmable superconducting processor known as Sycamore, taking approximately 200 seconds to sample one instance of a quantum circuit a million times, which would take a state-of-the-art supercomputer around ten thousand years to compute.
Abstract: The promise of quantum computers is that certain computational tasks might be executed exponentially faster on a quantum processor than on a classical processor1. A fundamental challenge is to build a high-fidelity processor capable of running quantum algorithms in an exponentially large computational space. Here we report the use of a processor with programmable superconducting qubits2-7 to create quantum states on 53 qubits, corresponding to a computational state-space of dimension 253 (about 1016). Measurements from repeated experiments sample the resulting probability distribution, which we verify using classical simulations. Our Sycamore processor takes about 200 seconds to sample one instance of a quantum circuit a million times-our benchmarks currently indicate that the equivalent task for a state-of-the-art classical supercomputer would take approximately 10,000 years. This dramatic increase in speed compared to all known classical algorithms is an experimental realization of quantum supremacy8-14 for this specific computational task, heralding a much-anticipated computing paradigm.

2,527 citations


Proceedings ArticleDOI
25 Jan 2019
TL;DR: In this paper, the realism of state-of-the-art image manipulations, and how difficult it is to detect them, either automatically or by humans, is examined.
Abstract: The rapid progress in synthetic image generation and manipulation has now come to a point where it raises significant concerns for the implications towards society. At best, this leads to a loss of trust in digital content, but could potentially cause further harm by spreading false information or fake news. This paper examines the realism of state-of-the-art image manipulations, and how difficult it is to detect them, either automatically or by humans. To standardize the evaluation of detection methods, we propose an automated benchmark for facial manipulation detection. In particular, the benchmark is based on Deep-Fakes, Face2Face, FaceSwap and NeuralTextures as prominent representatives for facial manipulations at random compression level and size. The benchmark is publicly available and contains a hidden test set as well as a database of over 1.8 million manipulated images. This dataset is over an order of magnitude larger than comparable, publicly available, forgery datasets. Based on this data, we performed a thorough analysis of data-driven forgery detectors. We show that the use of additional domain-specific knowledge improves forgery detection to unprecedented accuracy, even in the presence of strong compression, and clearly outperforms human observers.

917 citations


Journal ArticleDOI
TL;DR: This review explores the structure-property relationships of a library of non-fullerene acceptors, highlighting the important chemical modifications that have led to progress in the field and provides an outlook for future innovations in electron acceptors for use in organic photovoltaics.
Abstract: Fullerenes have formed an integral part of high performance organic solar cells over the last 20 years, however their inherent limitations in terms of synthetic flexibility, cost and stability have acted as a motivation to develop replacements; the so-called non-fullerene electron acceptors. A rapid evolution of such materials has taken place over the last few years, yielding a number of promising candidates that can exceed the device performance of fullerenes and provide opportunities to improve upon the stability and processability of organic solar cells. In this review we explore the structure–property relationships of a library of non-fullerene acceptors, highlighting the important chemical modifications that have led to progress in the field and provide an outlook for future innovations in electron acceptors for use in organic photovoltaics.

764 citations


Journal ArticleDOI
TL;DR: A range of effective interventions is available to support adequate nutrition and hydration in older persons in order to maintain or improve nutritional status and improve clinical course and quality of life.

700 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 Michailidou2, Kyriaki Michailidou1, 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: This paper highlights three different energy harvester models, namely, one linear model and two nonlinear models, and shows how WIPT designs differ for each of them in single-user and multi-user deployments, and identifies the fundamental tradeoff between conveying information and power wirelessly.
Abstract: Radio waves carry both energy and information simultaneously. Nevertheless, radio-frequency (RF) transmissions of these quantities have traditionally been treated separately. Currently, the community is experiencing a paradigm shift in wireless network design, namely, unifying wireless transmission of information and power so as to make the best use of the RF spectrum and radiation as well as the network infrastructure for the dual purpose of communicating and energizing. In this paper, we review and discuss recent progress in laying the foundations of the envisioned dual purpose networks by establishing a signal theory and design for wireless information and power transmission (WIPT) and identifying the fundamental tradeoff between conveying information and power wirelessly. We start with an overview of WIPT challenges and technologies, namely, simultaneous WIPT (SWIPT), wirelessly powered communication networks (WPCNs), and wirelessly powered backscatter communication (WPBC). We then characterize energy harvesters and show how WIPT signal and system designs crucially revolve around the underlying energy harvester model. To that end, we highlight three different energy harvester models, namely, one linear model and two nonlinear models, and show how WIPT designs differ for each of them in single-user and multi-user deployments. Topics discussed include rate-energy region characterization, transmitter and receiver architectures, waveform design, modulation, beamforming and input distribution optimizations, resource allocation, and RF spectrum use. We discuss and check the validity of the different energy harvester models and the resulting signal theory and design based on circuit simulations, prototyping, and experimentation. We also point out numerous directions that are promising for future research.

556 citations


Journal ArticleDOI
TL;DR: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke, but there were more clinically relevant nonmajor bleeding events in the dabig atran group.
Abstract: BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).

496 citations


Journal ArticleDOI
29 May 2019-Nature
TL;DR: It is shown that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis.
Abstract: The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs)1,2. However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage3-5. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1- destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

476 citations


Journal ArticleDOI
TL;DR: This Review discusses the basic concepts that underlie an effective design of reduced TiO2 photocatalysts for hydrogen production, and analysis of structure deformation and presence of unpaired electrons through electron paramagnetic resonance spectroscopy.
Abstract: Black TiO2 nanomaterials have recently emerged as promising candidates for solar-driven photocatalytic hydrogen production. Despite the great efforts to synthesize highly reduced TiO2, it is apparent that intermediate degree of reduction (namely, gray titania) brings about the formation of peculiar defective catalytic sites enabling cocatalyst-free hydrogen generation. A precise understanding of the structural and electronic nature of these catalytically active sites is still elusive, as well as the fundamental structure-activity relationships that govern formation of crystal defects, increased light absorption, charge separation, and photocatalytic activity. In this Review, we discuss the basic concepts that underlie an effective design of reduced TiO2 photocatalysts for hydrogen production such as (i) defects formation in reduced TiO2, (ii) analysis of structure deformation and presence of unpaired electrons through electron paramagnetic resonance spectroscopy, (iii) insights from surface science on electronic singularities due to defects, and (iv) the key differences between black and gray titania, that is, photocatalysts that require Pt-modification and cocatalyst-free photocatalytic hydrogen generation. Finally, future directions to improve the performance of reduced TiO2 photocatalysts are outlined.

Journal ArticleDOI
TL;DR: This article used an ensemble of up to five models to provide a consensus estimate for the ice thickness distribution of all the about 215,000 glaciers outside the Greenland and Antarctic ice sheets, which is equivalent to 0.32 m of sea-level change when the fraction of ice located below present-day sea level (roughly 15%) is subtracted.
Abstract: Knowledge of the ice thickness distribution of the world’s glaciers is a fundamental prerequisite for a range of studies. Projections of future glacier change, estimates of the available freshwater resources or assessments of potential sea-level rise all need glacier ice thickness to be accurately constrained. Previous estimates of global glacier volumes are mostly based on scaling relations between glacier area and volume, and only one study provides global-scale information on the ice thickness distribution of individual glaciers. Here we use an ensemble of up to five models to provide a consensus estimate for the ice thickness distribution of all the about 215,000 glaciers outside the Greenland and Antarctic ice sheets. The models use principles of ice flow dynamics to invert for ice thickness from surface characteristics. We find a total volume of 158 ± 41 × 103 km3, which is equivalent to 0.32 ± 0.08 m of sea-level change when the fraction of ice located below present-day sea level (roughly 15%) is subtracted. Our results indicate that High Mountain Asia hosts about 27% less glacier ice than previously suggested, and imply that the timing by which the region is expected to lose half of its present-day glacier area has to be moved forward by about one decade. The ice volume of glaciers outside the Greenland and Antarctic ice sheets totals about 158,000 km3, with about 27% less ice in High Mountain Asia than thought, according to multiple models that estimate ice thickness from surface characteristics.

Journal ArticleDOI
TL;DR: Anti-inflammatory cytokines counterbalance the chronic activation of innate and adaptive immune cells in rheumatoid arthritis anducing anti-inflammatory pathways and the resolution of inflammation is an attractive therapeutic option for patients with RA to achieve long-term disease control.
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a failure of spontaneous resolution of inflammation. Although the pro-inflammatory cytokines and mediators that trigger RA have been the focus of intense investigations, the regulatory and anti-inflammatory cytokines responsible for the suppression and resolution of disease in a context-dependent manner have been less well characterized. However, knowledge of the pathways that control the suppression and resolution of inflammation in RA is clinically relevant and conceptually important for understanding the pathophysiology of the disease and for the development of treatments that enable long-term remission. Cytokine-mediated processes such as the activation of T helper 2 cells by IL-4 and IL-13, the resolution of inflammation by IL-9, IL-5-induced eosinophil expansion, IL-33-mediated macrophage polarization, the production of IL-10 by regulatory B cells and IL-27-mediated suppression of lymphoid follicle formation are all involved in governing the regulation and resolution of inflammation in RA. By better understanding these immune-regulatory signalling pathways, new therapeutic strategies for RA can be envisioned that aim to balance and resolve, rather than suppress, inflammation.

Journal ArticleDOI
TL;DR: Since the publication of the first expert consensus document on computed tomography imaging before transcatheter aortic valve implantation (TAVI)/transcatheter valve replacement (TAVR) by the Society of Cardiovascular Computed Tomography (SCCT) in 2012, there has been tremendous
Abstract: Since the publication of the first expert consensus document on computed tomography imaging before transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR) by the Society of Cardiovascular Computed Tomography (SCCT) in 2012 [(1)][1], there has been tremendous

Journal ArticleDOI
TL;DR: An expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

Journal ArticleDOI
TL;DR: In this paper, a catalogue of white dwarf candidates selected from the second data release of Gaia (DR2) is presented, consisting of 486641 stars with calculated probability of being a white dwarf (PWD) for all Gaia sources that passed the initial selection.
Abstract: We present a catalogue of white dwarf candidates selected from the second data release of Gaia (DR2). We used a sample of spectroscopically confirmed white dwarfs from the Sloan Digital Sky Survey (SDSS) to map the entire space spanned by these objects in the Gaia Hertzsprung–Russell diagram. We then defined a set of cuts in absolute magnitude, colour, and a number of Gaia quality flags to remove the majority of contaminating objects. Finally, we adopt a method analogous to the one presented in our earlier SDSS photometric catalogues to calculate a probability of being a white dwarf (PWD) for all Gaia sources that passed the initial selection. The final catalogue is composed of 486641 stars with calculated PWD from which it is possible to select a sample of ≃260000 high-confidence white dwarf candidates in the magnitude range 8 7000 K, at high Galactic latitudes (|b| > 20°). However, the completeness drops at low Galactic latitudes, and the magnitude limit of the catalogue varies significantly across the sky as a function of Gaia’s scanning law. We also provide the list of objects within our sample with available SDSS spectroscopy. We use this spectroscopic sample to characterize the observed structure of the white dwarf distribution in the H–R diagram.

Journal ArticleDOI
TL;DR: This summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and priorities for research.

Journal ArticleDOI
TL;DR: A gentle introduction to deep learning in medical image processing is given, proceeding from theoretical foundations to applications, including general reasons for the popularity of deep learning, including several major breakthroughs in computer science.
Abstract: This paper tries to give a gentle introduction to deep learning in medical image processing, proceeding from theoretical foundations to applications. We first discuss general reasons for the popularity of deep learning, including several major breakthroughs in computer science. Next, we start reviewing the fundamental basics of the perceptron and neural networks, along with some fundamental theory that is often omitted. Doing so allows us to understand the reasons for the rise of deep learning in many application domains. Obviously medical image processing is one of these areas which has been largely affected by this rapid progress, in particular in image detection and recognition, image segmentation, image registration, and computer-aided diagnosis. There are also recent trends in physical simulation, modeling, and reconstruction that have led to astonishing results. Yet, some of these approaches neglect prior knowledge and hence bear the risk of producing implausible results. These apparent weaknesses highlight current limitations of deep ()learning. However, we also briefly discuss promising approaches that might be able to resolve these problems in the future.

Journal ArticleDOI
TL;DR: In this Review, Neurath delineates the cells, pathways and signals that contribute to the pathology of inflammatory bowel disease and the potential for therapeutic intervention.
Abstract: Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are characterized by uncontrolled activation of intestinal immune cells in a genetically susceptible host. Due to the progressive and destructive nature of the inflammatory process in IBD, complications such as fibrosis, stenosis or cancer are frequently observed, which highlights the need for effective anti-inflammatory therapy. Studies have identified altered trafficking of immune cells and pathogenic immune cell circuits as crucial drivers of mucosal inflammation and tissue destruction in IBD. A defective gut barrier and microbial dysbiosis induce such accumulation and local activation of immune cells, which results in a pro-inflammatory cytokine loop that overrides anti-inflammatory signals and causes chronic intestinal inflammation. This Review discusses pathogenic cytokine responses of immune cells as well as immune cell trafficking as a rational basis for new translational therapies in IBD.

Journal ArticleDOI
TL;DR: Non-redundant functions of the core transcription factors that mediate the epithelial–mesenchymal transition are described, and the conflicting results regarding their roles in this process are discussed.
Abstract: Epithelial-mesenchymal transition (EMT) is a crucial embryonic programme that is executed by various EMT transcription factors (EMT-TFs) and is aberrantly activated in cancer and other diseases. However, the causal role of EMT and EMT-TFs in different disease processes, especially cancer and metastasis, continues to be debated. In this Review, we identify and describe specific, non-redundant functions of the different EMT-TFs and discuss the reasons that may underlie disputes about EMT in cancer.

Journal ArticleDOI
07 Aug 2019-Nature
TL;DR: Analysis of macrophage subsets within joints reveals a population of CX3CR1+ tissue-resident macrophages that form a tight-junction-mediated barrier at the synovial lining, protecting the joint from the invasion of inflammatory cells.
Abstract: Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1− mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease. Analysis of macrophage subsets within joints reveals a population of CX3CR1+ tissue-resident macrophages that form a tight-junction-mediated barrier at the synovial lining, protecting the joint from the invasion of inflammatory cells.

Posted Content
TL;DR: Simulation results reveal that deploying large-scale IRSs in wireless systems is more efficient than increasing the antenna array size at the AP for enhancing both the spectral and the energy efficiency.
Abstract: Intelligent reflecting surfaces (IRSs) have received considerable attention from the wireless communications research community recently. In particular, as low-cost passive devices, IRSs enable the control of the wireless propagation environment, which is not possible in conventional wireless networks. To take full advantage of such IRS-assisted communication systems, both the beamformer at the access point (AP) and the phase shifts at the IRS need to be optimally designed. However, thus far, the optimal design is not well understood. In this paper, a point-to-point IRS-assisted multiple-input single-output (MISO) communication system is investigated. The beamformer at the AP and the IRS phase shifts are jointly optimized to maximize the spectral efficiency. Two efficient algorithms exploiting fixed point iteration and manifold optimization techniques, respectively, are developed for solving the resulting non-convex optimization problem. The proposed algorithms not only achieve a higher spectral efficiency but also lead to a lower computational complexity than the state-of-the-art approach. Simulation results reveal that deploying large-scale IRSs in wireless systems is more efficient than increasing the antenna array size at the AP for enhancing both the spectral and the energy efficiency.

Journal ArticleDOI
16 Jan 2019-Joule
TL;DR: In this article, the industrial viability of highly efficient OSCs based on several representative non-fullerene acceptors (NFAs) was investigated, and the most stable OSC exhibited PCE of ∼8% along with extrapolated T80 lifetime (80% of the initial PCE) of over 11,000hr under equivalent 1 sun illumination.

Journal ArticleDOI
TL;DR: Both theoretical and experimental results reveal that PN4N and PDCBT can interact strongly with the perovskite crystal, which effectively passivates the electronic surface trap states and suppresses the photoinduced halide segregation of CsPbI2 Br films.
Abstract: A synergic interface design is demonstrated for photostable inorganic mixed-halide perovskite solar cells (PVSCs) by applying an amino-functionalized polymer (PN4N) as cathode interlayer and a dopant-free hole-transporting polymer poly[5,5'-bis(2-butyloctyl)-(2,2'-bithiophene)-4,4'-dicarboxylate-alt-5,5'-2,2'-bithiophene] (PDCBT) as anode interlayer. First, the interfacial dipole formed at the cathode interface reduces the workfunction of SnO2 , while PDCBT with deeper-lying highest occupied molecular orbital (HOMO) level provides a better energy-level matching at the anode, leading to a significant enhancement in open-circuit voltage (Voc ) of the PVSCs. Second, the PN4N layer can also tune the surface wetting property to promote the growth of high-quality all-inorganic perovskite films with larger grain size and higher crystallinity. Most importantly, both theoretical and experimental results reveal that PN4N and PDCBT can interact strongly with the perovskite crystal, which effectively passivates the electronic surface trap states and suppresses the photoinduced halide segregation of CsPbI2 Br films. Therefore, the optimized CsPbI2 Br PVSCs exhibit reduced interfacial recombination with efficiency over 16%, which is one of the highest efficiencies reported for all-inorganic PVSCs. A high photostability with a less than 10% efficiency drop is demonstrated for the CsPbI2 Br PVSCs with dual interfacial modifications under continuous 1 sun equivalent illumination for 400 h.

Journal ArticleDOI
Bruce C.V. Campbell1, Bruce C.V. Campbell2, Henry Ma3, Henry Ma2  +264 moreInstitutions (15)
TL;DR: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo, and this increase in the rate of symptomatic intracerebral haemorrhage did not negate the overall net benefit of thrombolysis.

Journal ArticleDOI
TL;DR: Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A, and long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.
Abstract: PURPOSETotal neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established.PATIENTS AND ME...

Journal ArticleDOI
TL;DR: A number of core pathways and mechanisms of fibrosis, outlined in this Review, are shared across different tissues and might therefore present targets for general antifibrotic strategies and might enable the development of general antIFIBrotic compounds that are effective across different disease entities and organs.
Abstract: Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly associated with high morbidity and mortality. The medical need for effective antifibrotic therapies is thus very high. However, the extraordinarily high costs of drug development and the rare incidence of many fibrotic disorders hinder the development of targeted therapies for individual fibrotic diseases. A potential strategy to overcome this challenge is to target common mechanisms and core pathways that are of central pathophysiological relevance across different fibrotic diseases. The factors influencing susceptibility to and initiation of these diseases are often distinct, with disease-specific and organ-specific risk factors, triggers and sites of first injury. Fibrotic remodelling programmes with shared fibrotic signalling responses such as transforming growth factor-β (TGFβ), platelet-derived growth factor (PDGF), WNT and hedgehog signalling drive disease progression in later stages of fibrotic diseases. The convergence towards shared responses has consequences for drug development as it might enable the development of general antifibrotic compounds that are effective across different disease entities and organs. Technological advances, including new models, single-cell technologies and gene editing, could provide new insights into the pathogenesis of fibrotic diseases and the development of drugs for their treatment. A number of core pathways and mechanisms of fibrosis, outlined in this Review, are shared across different tissues and might therefore present targets for general antifibrotic strategies. Organ-specific and disease-specific differences in fibrotic diseases could also provide insights for drug development efforts.

Journal ArticleDOI
TL;DR: It is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSFAβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.
Abstract: The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer’s Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

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TL;DR: This paper investigates the resource allocation algorithm design for multicarrier solar-powered unmanned aerial vehicle (UAV) communication systems and proposes a low-complexity iterative suboptimal online scheme based on the successive convex approximation.
Abstract: In this paper, we investigate the resource allocation algorithm design for multicarrier solar-powered unmanned aerial vehicle (UAV) communication systems. In particular, the UAV is powered by the solar energy enabling sustainable communication services to multiple ground users. We study the joint design of the 3D aerial trajectory and the wireless resource allocation for maximization of the system sum throughput over a given time period. As a performance benchmark, we first consider an off-line resource allocation design assuming non-causal knowledge of the channel gains. The algorithm design is formulated as a mixed-integer non-convex optimization problem taking into account the aerodynamic power consumption, solar energy harvesting, a finite energy storage capacity, and the quality-of-service requirements of the users. Despite the non-convexity of the optimization problem, we solve it optimally by applying monotonic optimization to obtain the optimal 3D-trajectory and the optimal power and subcarrier allocation policy. Subsequently, we focus on the online algorithm design that only requires real-time and statistical knowledge of the channel gains. The optimal online resource allocation algorithm is motivated by the off-line scheme and entails a high computational complexity. Hence, we also propose a low-complexity iterative suboptimal online scheme based on the successive convex approximation. Our simulation results reveal that both the proposed online schemes closely approach the performance of the benchmark off-line scheme and substantially outperform two baseline schemes. Furthermore, our results unveil the tradeoff between solar energy harvesting and power-efficient communication. In particular, the solar-powered UAV first climbs up to a high altitude to harvest a sufficient amount of solar energy and then descends again to a lower altitude to reduce the path loss of the communication links to the users it serves.

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TL;DR: In this paper, the enforcement of a CO2 tax, stringent regulations, and investment in renewables are some of the mitigation strategies currently in place for reducing CO2 emissions in the world.
Abstract: Reducing CO2 emissions is an urgent global priority. The enforcement of a CO2 tax, stringent regulations, and investment in renewables are some of the mitigation strategies currently in place. For ...