Showing papers by "Humboldt University of Berlin published in 2016"
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2 +679 more•Institutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.
1,533 citations
TL;DR: This survey unroll and structure the manyfold results and research directions of Bitcoin, and deduce the fundamental structures and insights at the core of the Bitcoin protocol and its applications.
Abstract: Besides attracting a billion dollar economy, Bitcoin revolutionized the field of digital currencies and influenced many adjacent areas. This also induced significant scientific interest. In this survey, we unroll and structure the manyfold results and research directions. We start by introducing the Bitcoin protocol and its building blocks. From there we continue to explore the design space by discussing existing contributions and results. In the process, we deduce the fundamental structures and insights at the core of the Bitcoin protocol and its applications. As we show and discuss, many key ideas are likewise applicable in various other fields, so that their impact reaches far beyond Bitcoin itself.
1,193 citations
Ghent University1, Forschungszentrum Jülich2, Aalto University3, Åbo Akademi University4, Vienna University of Technology5, Duke University6, University of Grenoble7, École Polytechnique Fédérale de Lausanne8, Durham University9, International School for Advanced Studies10, Max Planck Society11, Uppsala University12, Fritz Haber Institute of the Max Planck Society13, Humboldt University of Berlin14, Technical University of Denmark15, National Institute of Standards and Technology16, University of Udine17, Université catholique de Louvain18, University of Basel19, Harvard University20, University of California, Davis21, Rutgers University22, University of York23, Wake Forest University24, Science and Technology Facilities Council25, University of Oxford26, University of Vienna27, Leibniz Institute for Neurobiology28, Dresden University of Technology29, Radboud University Nijmegen30, University of Tokyo31, Centre national de la recherche scientifique32, University of Cambridge33, Royal Holloway, University of London34, University of California, Santa Barbara35, University of Luxembourg36, Los Alamos National Laboratory37, Harbin Institute of Technology38
TL;DR: A procedure to assess the precision of DFT methods was devised and used to demonstrate reproducibility among many of the most widely used DFT codes, demonstrating that the precisionof DFT implementations can be determined, even in the absence of one absolute reference code.
Abstract: The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.
1,141 citations
TL;DR: The most important advances with regard to fundamental research, sensing mechanisms, and application of nanostructured materials for room-temperature conductometric sensor devices are reviewed here and particular emphasis is given to the relation between the nanostructure and sensor properties in an attempt to address structure-property correlations.
Abstract: Sensor technology has an important effect on many aspects in our society, and has gained much progress, propelled by the development of nanoscience and nanotechnology. Current research efforts are directed toward developing high-performance gas sensors with low operating temperature at low fabrication costs. A gas sensor working at room temperature is very appealing as it provides very low power consumption and does not require a heater for high-temperature operation, and hence simplifies the fabrication of sensor devices and reduces the operating cost. Nanostructured materials are at the core of the development of any room-temperature sensing platform. The most important advances with regard to fundamental research, sensing mechanisms, and application of nanostructured materials for room-temperature conductometric sensor devices are reviewed here. Particular emphasis is given to the relation between the nanostructure and sensor properties in an attempt to address structure-property correlations. Finally, some future research perspectives and new challenges that the field of room-temperature sensors will have to address are also discussed.
1,096 citations
Stanford University1, Illinois Institute of Technology2, University of Melbourne3, Greifswald University Hospital4, University of Münster5, University of Marburg6, VU University Medical Center7, University of Göttingen8, Humboldt University of Berlin9, Harvard University10, University Medical Center Groningen11, University of Cape Town12, Max Planck Society13, University of Southern California14
TL;DR: Three-dimensional brain magnetic resonance imaging data was meta-analyzed to identify subcortical brain volumes that robustly discriminate major depressive disorder patients from healthy controls and showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
Abstract: The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
759 citations
TL;DR: Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both.
725 citations
TL;DR: This report provides national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.
522 citations
TL;DR: An improved understanding is required of just how the admixture of dopant molecules to organic semiconductors does affect the density of states, and how this will provide viable guidelines for synthetic and supramolecular chemistry that will enable further technological advances in organic and hybrid organic/inorganic devices.
Abstract: ConspectusToday’s information society depends on our ability to controllably dope inorganic semiconductors, such as silicon, thereby tuning their electrical properties to application-specific demands. For optoelectronic devices, organic semiconductors, that is, conjugated polymers and molecules, have emerged as superior alternative owing to the ease of tuning their optical gap through chemical variability and their potential for low-cost, large-area processing on flexible substrates. There, the potential of molecular electrical doping for improving the performance of, for example, organic light-emitting devices or organic solar cells has only recently been established. The doping efficiency, however, remains conspicuously low, highlighting the fact that the underlying mechanisms of molecular doping in organic semiconductors are only little understood compared with their inorganic counterparts.Here, we review the broad range of phenomena observed upon molecularly doping organic semiconductors and identify ...
504 citations
TL;DR: In this paper, an isotropic, unbroken power-law flux with a normalization at 100 TeV neutrino energy of (0.90 -0.27 +0.30) × 10-18 Gev-1 cm-2 s-1 sr-1 and a hard spectral index of γ = 2.13 ± 0.13.
Abstract: The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 194 TeV and 7.8 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at 5.6s significance. The data are well described by an isotropic, unbroken power-law flux with a normalization at 100 TeV neutrino energy of (0.90 -0.27 +0.30) × 10-18 Gev-1 cm-2 s-1 sr-1and a hard spectral index of γ = 2.13 ± 0.13. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest-energy event observed has a reconstructed muon energy of (4.5 ± 1.2) PeV which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known γ-ray sources was found. Using the high statistics of atmospheric neutrinos we report the current best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below 1.06 in units of the flux normalization of the model in Enberg et al.
TL;DR: In this article, the authors present an international consensus on how urban ecology can advance along multiple research directions and suggest pathways for advancing urban ecology research to support the goals of improving urban sustainability and resilience, conserving urban biodiversity, and promoting human well-being on an urbanizing planet.
Abstract: Urban ecology is a field encompassing multiple disciplines and practical applications and has grown rapidly. However, the field is heterogeneous as a global inquiry with multiple theoretical and conceptual frameworks, variable research approaches, and a lack of coordination among multiple schools of thought and research foci. Here, we present an international consensus on how urban ecology can advance along multiple research directions. There is potential for the field to mature as a holistic, integrated science of urban systems. Such an integrated science could better inform decisionmakers who need increased understanding of complex relationships among social, ecological, economic, and built infrastructure systems. To advance the field requires conceptual synthesis, knowledge and data sharing, cross-city comparative research, new intellectual networks, and engagement with additional disciplines. We consider challenges and opportunities for understanding dynamics of urban systems. We suggest pathways for advancing urban ecology research to support the goals of improving urban sustainability and resilience, conserving urban biodiversity, and promoting human well-being on an urbanizing planet.
Wouter van Rheenen1, Aleksey Shatunov2, Annelot M. Dekker1, Russell L. McLaughlin3 +184 more•Institutions (54)
TL;DR: Evidence of ALS being a complex genetic trait with a polygenic architecture is established and the SNP-based heritability is estimated at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%).
Abstract: To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
TL;DR: In this article, the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015 was evaluated using the Monte Carlo simulations.
Abstract: This article documents the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9% while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%.
A. Abramowski1, Felix Aharonian2, Faical Ait Benkhali2, A. G. Akhperjanian +226 more•Institutions (28)
TL;DR: Deep γ-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre are reported, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy, and it is proposed that the supermassive black hole Sagittarius A* is linked to this PeVatron.
Abstract: Galactic cosmic rays reach energies of at least a few petaelectronvolts(1) (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators ('PeVatrons'), b ...
TL;DR: These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
Abstract: Objectives Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. Methods In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of 'management' and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. Results The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. Conclusions These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
TL;DR: In this paper, an independent b-tagging algorithm based on the reconstruction of muons inside jets as well as the b tagging algorithm used in the online trigger are also presented.
Abstract: The identification of jets containing b hadrons is important for the physics programme of the ATLAS experiment at the Large Hadron Collider. Several algorithms to identify jets containing b hadrons are described, ranging from those based on the reconstruction of an inclusive secondary vertex or the presence of tracks with large impact parameters to combined tagging algorithms making use of multi-variate discriminants. An independent b-tagging algorithm based on the reconstruction of muons inside jets as well as the b-tagging algorithm used in the online trigger are also presented. The b-jet tagging efficiency, the c-jet tagging efficiency and the mistag rate for light flavour jets in data have been measured with a number of complementary methods. The calibration results are presented as scale factors defined as the ratio of the efficiency (or mistag rate) in data to that in simulation. In the case of b jets, where more than one calibration method exists, the results from the various analyses have been combined taking into account the statistical correlation as well as the correlation of the sources of systematic uncertainty.
Potsdam Institute for Climate Impact Research1, University of Maryland, College Park2, Massachusetts Institute of Technology3, Met Office4, Humboldt University of Berlin5, Delft University of Technology6, Japan Agency for Marine-Earth Science and Technology7, University of Washington8, Dalhousie University9, University of Chicago10, Columbia University11, Catalan Institution for Research and Advanced Studies12, Autonomous University of Barcelona13, University of Nottingham14, Catalan Institute for Water Research15, Goethe University Frankfurt16, Utrecht University17, Uppsala University18, United Nations Environment Programme19, Wageningen University and Research Centre20, Durham University21, Auburn University22, Chinese Academy of Sciences23
TL;DR: In Paris, France, December 2015, the Conference of the Parties (COP) to the United Nations Framework Concerning on Climate Change (UNFCCC) invited the Inter- governmental Panel on Climate change (IPCC).
Abstract: In Paris, France, December 2015, the Conference of the Parties (COP) to the United Nations Framework Con- vention on Climate Change (UNFCCC) invited the Inter- governmental Panel on Climate Change ...
TL;DR: In this article, the authors provide a systematic synthesis of 144 studies that identify the proximate and underlying drivers of landscape change across Europe and find that land abandonment/extensification is the most prominent (62% of cases) among multiple proximate drivers.
TL;DR: Whether microplastics can be ingested and whether their presence causes adverse effects after short-term exposure are investigated and underline that, considering high concentrations, microplastic particles can already induce adverse effects in limnic zooplankton.
TL;DR: In this paper, the authors assess green space availability in 299 EU cities according to land use and a population data grid and conclude that UGS availability is an important indicator to navigate urban complexity to improve human health and wellbeing but is only one component of the intricate social-ecological interactions within cities.
Oklahoma State University Center for Health Sciences1, Stony Brook University2, University of Texas at Austin3, Ohio University4, University of Missouri5, Hull York Medical School6, Sam Houston State University7, University of Toronto8, University of Vienna9, Humboldt University of Berlin10, University of Utah11, University of Chicago12, Villanova University13, Brown University14
TL;DR: A critical review of the recent contributions to iodine‐based, contrast‐enhanced CT research is provided to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies.
Abstract: Morphologists have historically had to rely on destructive procedures to visualize the three-dimensional (3-D) anatomy of animals. More recently, however, non-destructive techniques have come to the forefront. These include X-ray computed tomography (CT), which has been used most commonly to examine the mineralized, hard-tissue anatomy of living and fossil metazoans. One relatively new and potentially transformative aspect of current CT-based research is the use of chemical agents to render visible, and differentiate between, soft-tissue structures in X-ray images. Specifically, iodine has emerged as one of the most widely used of these contrast agents among animal morphologists due to its ease of handling, cost effectiveness, and differential affinities for major types of soft tissues. The rapid adoption of iodine-based contrast agents has resulted in a proliferation of distinct specimen preparations and scanning parameter choices, as well as an increasing variety of imaging hardware and software preferences. Here we provide a critical review of the recent contributions to iodine-based, contrast-enhanced CT research to enable researchers just beginning to employ contrast enhancement to make sense of this complex new landscape of methodologies. We provide a detailed summary of recent case studies, assess factors that govern success at each step of the specimen storage, preparation, and imaging processes, and make recommendations for standardizing both techniques and reporting practices. Finally, we discuss potential cutting-edge applications of diffusible iodine-based contrast-enhanced computed tomography (diceCT) and the issues that must still be overcome to facilitate the broader adoption of diceCT going forward.
TL;DR: RiboTaper is a powerful method for comprehensive de novo identification of actively used ORFs from Ribo-seq data and finds distinct ribosomal signatures for several hundred upstream ORFs and ORFs in annotated noncoding genes (ncORFs).
Abstract: RNA-sequencing protocols can quantify gene expression regulation from transcription to protein synthesis. Ribosome profiling (Ribo-seq) maps the positions of translating ribosomes over the entire transcriptome. We have developed RiboTaper (available at https://ohlerlab.mdc-berlin.de/software/), a rigorous statistical approach that identifies translated regions on the basis of the characteristic three-nucleotide periodicity of Ribo-seq data. We used RiboTaper with deep Ribo-seq data from HEK293 cells to derive an extensive map of translation that covered open reading frame (ORF) annotations for more than 11,000 protein-coding genes. We also found distinct ribosomal signatures for several hundred upstream ORFs and ORFs in annotated noncoding genes (ncORFs). Mass spectrometry data confirmed that RiboTaper achieved excellent coverage of the cellular proteome. Although dozens of novel peptide products were validated in this manner, few of the currently annotated long noncoding RNAs appeared to encode stable polypeptides. RiboTaper is a powerful method for comprehensive de novo identification of actively used ORFs from Ribo-seq data.
TL;DR: The results revealed that the initial size of the urban heat island had significant influence on SUHIM, and cities of cooler climates and cities with higher shares of urban green spaces were more affected by additional heat during heat waves.
TL;DR: It is found that Ca2+ activity in the apical dendrites of a subset of layer 5 pyramidal neurons in primary somatosensory cortex (S1) in mice is correlated with the threshold for perceptual detection of whisker deflections.
Abstract: There is as yet no consensus concerning the neural basis of perception and how it operates at a mechanistic level. We found that Ca2+ activity in the apical dendrites of a subset of layer 5 (L5) pyramidal neurons in primary somatosensory cortex (S1) in mice is correlated with the threshold for perceptual detection of whisker deflections. Manipulating the activity of apical dendrites shifted the perceptual threshold, demonstrating that an active dendritic mechanism is causally linked to perceptual detection.
TL;DR: The methods employed in the ATLAS experiment to correct for the impact of pile-up on jet energy and jet shapes, and for the presence of spurious additional jets, are described, with a primary focus on the large 20.3 kg-1 data sample.
Abstract: The large rate of multiple simultaneous protonproton interactions, or pile-up, generated by the Large Hadron Collider in Run 1 required the development of many new techniques to mitigate the advers ...
Lawrence Berkeley National Laboratory1, Humboldt University of Berlin2, Umeå University3, SLAC National Accelerator Laboratory4, University of Oxford5, Brookhaven National Laboratory6, Howard Hughes Medical Institute7, Stanford University8, Rutherford Appleton Laboratory9, University of California, Berkeley10, Uppsala University11
TL;DR: Ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states, and this approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O–O bond formation mechanisms.
Abstract: Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S0 to S4), in which S1 is the dark-stable state and S3 is the last semi-stable state before O-O bond formation and O2 evolution. A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S1), two-flash illuminated (2F; S3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II. Although the recent 1.95 A resolution structure of PS II at cryogenic temperature using an XFEL provided a damage-free view of the S1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site. This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.
University of Regensburg1, Goethe University Frankfurt2, University of Padua3, Ludwig Maximilian University of Munich4, Heidelberg University5, University of Jena6, University of Mainz7, University of Alberta8, Leiden University9, Sahlgrenska University Hospital10, University of Edinburgh11, Centre Hospitalier Universitaire de Nice12, University of Münster13, Université de Montréal14, University of Duisburg-Essen15, University of Tübingen16, University of Genoa17, University of Cambridge18, University of Oslo19, University of Kiel20, Karolinska University Hospital21, Helsinki University Central Hospital22, Medical University of Vienna23, Katholieke Universiteit Leuven24, Innsbruck Medical University25, Leipzig University26, University of Sydney27, Hannover Medical School28, Ghent University Hospital29, Mario Negri Institute for Pharmacological Research30, Cliniques Universitaires Saint-Luc31, Humboldt University of Berlin32
TL;DR: This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC and reveals that low-risk, rather than high- risk, patients benefited most from sirolimus; furthermore, younger recipients (age ⩽60) also benefited, as well siro Limus monotherapy patients.
Abstract: Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.
TL;DR: A liquid crystalline polymer film doped with a visible light responsive fluorinated azobenzene capable of continuous chaotic oscillatory motion when exposed to ambient sunlight in air is described.
Abstract: Nature provides much inspiration for the design of materials capable of motion upon exposure to external stimuli, and many examples of such active systems have been created in the laboratory. However, to achieve continuous motion driven by an unchanging, constant stimulus has proven extremely challenging. Here we describe a liquid crystalline polymer film doped with a visible light responsive fluorinated azobenzene capable of continuous chaotic oscillatory motion when exposed to ambient sunlight in air. The presence of simultaneous illumination by blue and green light is necessary for the oscillating behaviour to occur, suggesting that the dynamics of continuous forward and backward switching are causing the observed effect. Our work constitutes an important step towards the realization of autonomous, persistently self-propelling machines and self-cleaning surfaces powered by sunlight.
TL;DR: In this article, a framework for mapping and assessing the relationships between ecosystem services (ES) capacity, flow and demand with a focus on the identification of unsatisfied demand is presented.