Showing papers by "Shanghai Jiao Tong University published in 2015"

Efficient and stable large-area perovskite solar cells with inorganic charge extraction layers

Abstract: The recent dramatic rise in power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) has triggered intense research worldwide. However, high PCE values have often been reached with poor stability at an illuminated area of typically less than 0.1 square centimeter. We used heavily doped inorganic charge extraction layers in planar PSCs to achieve very rapid carrier extraction, even with 10- to 20-nanometer-thick layers, avoiding pinholes and eliminating local structural defects over large areas. The robust inorganic nature of the layers allowed for the fabrication of PSCs with an aperture area >1 square centimeter that have a PCE >15%, as certified by an accredited photovoltaic calibration laboratory. Hysteresis in the current-voltage characteristics was eliminated; the PSCs were stable, with >90% of the initial PCE remaining after 1000 hours of light soaking.

Hierarchical Convolutional Features for Visual Tracking

Abstract: Visual object tracking is challenging as target objects often undergo significant appearance changes caused by deformation, abrupt motion, background clutter and occlusion. In this paper, we exploit features extracted from deep convolutional neural networks trained on object recognition datasets to improve tracking accuracy and robustness. The outputs of the last convolutional layers encode the semantic information of targets and such representations are robust to significant appearance variations. However, their spatial resolution is too coarse to precisely localize targets. In contrast, earlier convolutional layers provide more precise localization but are less invariant to appearance changes. We interpret the hierarchies of convolutional layers as a nonlinear counterpart of an image pyramid representation and exploit these multiple levels of abstraction for visual tracking. Specifically, we adaptively learn correlation filters on each convolutional layer to encode the target appearance. We hierarchically infer the maximum response of each layer to locate targets. Extensive experimental results on a largescale benchmark dataset show that the proposed algorithm performs favorably against state-of-the-art methods.

Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis.

Abstract: Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis

Combined Measurement of the Higgs Boson Mass in pp Collisions at √s=7 and 8 TeV with the ATLAS and CMS Experiments

Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Abstract: Summary Background We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. Methods Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. Findings Median follow-up in LUX-Lung 3 was 41 months (IQR 35–44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31–37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28·2 months (95% CI 24·6–33·6) in the afatinib group and 28·2 months (20·7–33·2) in the pemetrexed-cisplatin group (HR 0·88, 95% CI 0·66–1·17, p=0·39). In LUX-Lung 6, median overall survival was 23·1 months (95% CI 20·4–27·3) in the afatinib group and 23·5 months (18·0–25·6) in the gemcitabine-cisplatin group (HR 0·93, 95% CI 0·72–1·22, p=0·61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33·3 months (95% CI 26·8–41·5) in the afatinib group versus 21·1 months (16·3–30·7) in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, p=0·0015); in LUX-Lung 6, it was 31·4 months (95% CI 24·2–35·3) versus 18·4 months (14·6–25·6), respectively (HR 0·64, 95% CI 0·44–0·94, p=0·023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27·6 months (19·8–41·7) in the afatinib group versus 40·3 months (24·3–not estimable) in the chemotherapy group (HR 1·30, 95% CI 0·80–2·11, p=0·29); in LUX-Lung 6, it was 19·6 months (95% CI 17·0–22·1) versus 24·3 months (19·0–27·0), respectively (HR 1·22, 95% CI 0·81–1·83, p=0·34). In both trials, the most common afatinib-related grade 3–4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3–4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3–4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). Interpretation Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials. Funding Boehringer Ingelheim.

Epitaxial growth of two-dimensional stanene

Abstract: Following the first experimental realization of graphene, other ultrathin materials with unprecedented electronic properties have been explored, with particular attention given to the heavy group-IV elements Si, Ge and Sn. Two-dimensional buckled Si-based silicene has been recently realized by molecular beam epitaxy growth, whereas Ge-based germanene was obtained by molecular beam epitaxy and mechanical exfoliation. However, the synthesis of Sn-based stanene has proved challenging so far. Here, we report the successful fabrication of 2D stanene by molecular beam epitaxy, confirmed by atomic and electronic characterization using scanning tunnelling microscopy and angle-resolved photoemission spectroscopy, in combination with first-principles calculations. The synthesis of stanene and its derivatives will stimulate further experimental investigation of their theoretically predicted properties, such as a 2D topological insulating behaviour with a very large bandgap, and the capability to support enhanced thermoelectric performance, topological superconductivity and the near-room-temperature quantum anomalous Hall effect.

Cross-scene crowd counting via deep convolutional neural networks

Abstract: Cross-scene crowd counting is a challenging task where no laborious data annotation is required for counting people in new target surveillance crowd scenes unseen in the training set. The performance of most existing crowd counting methods drops significantly when they are applied to an unseen scene. To address this problem, we propose a deep convolutional neural network (CNN) for crowd counting, and it is trained alternatively with two related learning objectives, crowd density and crowd count. This proposed switchable learning approach is able to obtain better local optimum for both objectives. To handle an unseen target crowd scene, we present a data-driven method to finetune the trained CNN model for the target scene. A new dataset including 108 crowd scenes with nearly 200,000 head annotations is introduced to better evaluate the accuracy of cross-scene crowd counting methods. Extensive experiments on the proposed and another two existing datasets demonstrate the effectiveness and reliability of our approach.

Investigating Critical Frequency Bands and Channels for EEG-Based Emotion Recognition with Deep Neural Networks

Abstract: To investigate critical frequency bands and channels, this paper introduces deep belief networks (DBNs) to constructing EEG-based emotion recognition models for three emotions: positive, neutral and negative. We develop an EEG dataset acquired from 15 subjects. Each subject performs the experiments twice at the interval of a few days. DBNs are trained with differential entropy features extracted from multichannel EEG data. We examine the weights of the trained DBNs and investigate the critical frequency bands and channels. Four different profiles of 4, 6, 9, and 12 channels are selected. The recognition accuracies of these four profiles are relatively stable with the best accuracy of 86.65%, which is even better than that of the original 62 channels. The critical frequency bands and channels determined by using the weights of trained DBNs are consistent with the existing observations. In addition, our experiment results show that neural signatures associated with different emotions do exist and they share commonality across sessions and individuals. We compare the performance of deep models with shallow models. The average accuracies of DBN, SVM, LR, and KNN are 86.08%, 83.99%, 82.70%, and 72.60%, respectively.

Exploring atomic defects in molybdenum disulphide monolayers

Abstract: Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment–theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 1013 cm−2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices. Imperfections can greatly alter a material’s properties. Here, the authors investigate the influence of point defects on the electronic structure, charge-carrier mobility and optical absorption of molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition.

Long-term correlation tracking

Abstract: In this paper, we address the problem of long-term visual tracking where the target objects undergo significant appearance variation due to deformation, abrupt motion, heavy occlusion and out-of-view. In this setting, we decompose the task of tracking into translation and scale estimation of objects. We show that the correlation between temporal context considerably improves the accuracy and reliability for translation estimation, and it is effective to learn discriminative correlation filters from the most confident frames to estimate the scale change. In addition, we train an online random fern classifier to re-detect objects in case of tracking failure. Extensive experimental results on large-scale benchmark datasets show that the proposed algorithm performs favorably against state-of-the-art methods in terms of efficiency, accuracy, and robustness.

Superconductivity above 100 K in single-layer FeSe films on doped SrTiO3

Abstract: Monolayer iron selenide grown on SrTiO3 has recently gained attention due to suggestive evidence it superconducts at high temperature. In situ electrical transport measurements now reveal a transition temperature above 100 K.

Decision tree methods: applications for classification and prediction.

Abstract: Decision tree methodology is a commonly used data mining method for establishing classification systems based on multiple covariates or for developing prediction algorithms for a target variable. This method classifies a population into branch-like segments that construct an inverted tree with a root node, internal nodes, and leaf nodes. The algorithm is non-parametric and can efficiently deal with large, complicated datasets without imposing a complicated parametric structure. When the sample size is large enough, study data can be divided into training and validation datasets. Using the training dataset to build a decision tree model and a validation dataset to decide on the appropriate tree size needed to achieve the optimal final model. This paper introduces frequently used algorithms used to develop decision trees (including CART, C4.5, CHAID, and QUEST) and describes the SPSS and SAS programs that can be used to visualize tree structure.

Sparse whole-genome sequencing identifies two loci for major depressive disorder

Abstract: Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene.

Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice

Abstract: Structural disruption of gut microbiota and associated inflammation are considered important etiological factors in high fat diet (HFD)-induced metabolic syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I-4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I-2494 (BA), were individually administered to HFD-fed mice (10(8) cells day(-1)) for 12 weeks. Each strain attenuated weight gain and macrophage infiltration into epididymal adipose tissue and markedly improved glucose-insulin homeostasis and hepatic steatosis. Weighted UniFrac principal coordinate analysis based on 454 pyrosequencing of fecal bacterial 16S rRNA genes showed that the probiotic strains shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean mice fed a normal (chow) diet. Redundancy analysis revealed that abundances of 83 operational taxonomic units (OTUs) were altered by probiotics. Forty-nine altered OTUs were significantly correlated with one or more host MS parameters and were designated 'functionally relevant phylotypes'. Thirteen of the 15 functionally relevant OTUs that were negatively correlated with MS phenotypes were promoted, and 26 of the 34 functionally relevant OTUs that were positively correlated with MS were reduced by at least one of the probiotics, but each strain changed a distinct set of functionally relevant OTUs. LC and LR increased cecal acetate but did not affect circulating lipopolysaccharide-binding protein; in contrast, BA did not increase acetate but significantly decreased adipose and hepatic tumor necrosis factor-α gene expression. These results suggest that Lactobacillus and Bifidobacterium differentially attenuate obesity comorbidities in part through strain-specific impacts on MS-associated phylotypes of gut microbiota in mice.

Core-shell structured high-k polymer nanocomposites for energy storage and dielectric applications.

Abstract: High-k polymer nanocomposites have considerable potential in energy storage and dielectric applications because of their ease of processing, flexibility, and low cost. Core-shell nanoarchitecture strategies are versatile and powerful tools for the design and synthesis of advanced high-k polymer nanocomposites. Recent and in-progress state-of-the-art advancements in the application of core-shell nanoarchitecture strategies to design and prepare high-k polymer nanocomposites are summarized. Special focus is directed to emphasizing their advantages over conventional melt-mixing and solution-mixing methods: first, homogeneous nanoparticle dispersion can be easily achieved even in highly loaded nanocomposites; second, the dielectric constant of the nanocomposites can be effectively enhanced and meanwhile the high breakdown strength can be well-preserved; third, for nanocomposites filled with electrically conductive nanoparticles, dielectric loss can be effectively surpressed, and meanwhile a high dielectric constant can be achieved. In addition, fundamental insights into the roles of the interfaces on the dielectric properties of the nanocomposites can be probed. The last part of the article is concluded with current problems and future perspectives of utilizing the core-shell nanoarchitecture strategies for the development of high-k polymer nanocomposites.

A Bioinspired, Reusable, Paper‐Based System for High‐Performance Large‐Scale Evaporation

Abstract: A bioinspired, reusable, paper-based gold-nanoparticle film is fabricated by depositing an as-prepared gold-nanoparticle thin film on airlaid paper. This paper-based system with enhanced surface roughness and low thermal conductivity exhibits increased efficiency of evaporation, scale-up potential, and proven reusability. It is also demonstrated to be potentially useful in seawater desalination.

Minimum Information about a Biosynthetic Gene cluster.

Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Neutrino Physics with JUNO

Abstract: The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy as a primary physics goal. It is also capable of observing neutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, solar neutrinos, as well as exotic searches such as nucleon decays, dark matter, sterile neutrinos, etc. We present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. By detecting reactor antineutrinos from two power plants at 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4 sigma significance with six years of running. The measurement of antineutrino spectrum will also lead to the precise determination of three out of the six oscillation parameters to an accuracy of better than 1\%. Neutrino burst from a typical core-collapse supernova at 10 kpc would lead to ~5000 inverse-beta-decay events and ~2000 all-flavor neutrino-proton elastic scattering events in JUNO. Detection of DSNB would provide valuable information on the cosmic star-formation rate and the average core-collapsed neutrino energy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400 events per year, significantly improving the statistics of existing geoneutrino samples. The JUNO detector is sensitive to several exotic searches, e.g. proton decay via the $p\to K^++\bar u$ decay channel. The JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.

Visible-Light-Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives

Abstract: Visible-light-induced radical decarboxylative functionalization of carboxylic acids and their derivatives has recently received considerable attention as a novel and efficient method to create CC and CX bonds. Generally, this visible-light-promoted decarboxylation process can smoothly occur under mild reaction conditions with a broad range of substrates and an excellent functional-group tolerance. The radical species formed from the decarboxylation step can participate in not only single photocatalytic transformations, but also dual-catalytic cross-coupling reactions by combining photoredox catalysis with other catalytic processes. Recent advances in this research area are discussed herein.

Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.

Abstract: Importance Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. Objective To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. Design, Setting, and Participants The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. Interventions Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10 348) or a tablet containing enalapril, 10 mg, alone (n = 10 354). Main Outcomes and Measures The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. Results During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril–folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril–folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril–folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril–folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. Conclusions and Relevance Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. Trial Registration clinicaltrials.gov Identifier:NCT00794885

Truly Fluorescent Excitation-Dependent Carbon Dots and Their Applications in Multicolor Cellular Imaging and Multidimensional Sensing

Abstract: Truly fluorescent excitation-dependent carbon dots are prepared, and the relationship between their chemical composition and fluorescent emission is discussed. Furthermore, potential applications of the as-prepared carbon dots to multicolor bio-labeling and multidimodal sensing are demonstrated.

Using free energy principle for blind image quality assessment

Abstract: In this paper we propose a new no-reference (NR) image quality assessment (IQA) metric using the recently revealed free-energy-based brain theory and classical human visual system (HVS)-inspired features. The features used can be divided into three groups. The first involves the features inspired by the free energy principle and the structural degradation model. Furthermore, the free energy theory also reveals that the HVS always tries to infer the meaningful part from the visual stimuli. In terms of this finding, we first predict an image that the HVS perceives from a distorted image based on the free energy theory, then the second group of features is composed of some HVS-inspired features (such as structural information and gradient magnitude) computed using the distorted and predicted images. The third group of features quantifies the possible losses of “naturalness” in the distorted image by fitting the generalized Gaussian distribution to mean subtracted contrast normalized coefficients. After feature extraction, our algorithm utilizes the support vector machine based regression module to derive the overall quality score. Experiments on LIVE, TID2008, CSIQ, IVC, and Toyama databases confirm the effectiveness of our introduced NR IQA metric compared to the state-of-the-art.

Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial

Abstract: Summary Background In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. Methods In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [ vs ≥18 months]) to receive oral regorafenib 160 mg once daily or placebo on days 1–21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Findings Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3–12·2), overall survival was significantly better with regorafenib than it was with placebo (hazard ratio 0·55, 95% CI 0·40–0·77, one-sided p=0·00016; median overall survival 8·8 months [95% CI 7·3–9·8] in the regorafenib group vs 6·3 months [4·8–7·6] in the placebo group). Drug-related adverse events occurred in 132 (97%) of 136 regorafenib recipients and 31 (46%) of 68 placebo recipients. The most frequent grade 3 or higher regorafenib-related adverse events were hand–foot skin reaction (22 [16%] of 136 patients in the regorafenib group vs none in the placebo group), hypertension (15 [11%] vs two [3%] of 68 patients in the placebo group), hyperbilirubinaemia (nine [7%] vs one [1%]), hypophosphataemia (nine [7%] vs none), alanine aminotransferase concentration increases (nine [7%] vs none), aspartate aminotransferase concentration increases (eight [6%] vs none), lipase concentration increases (six [4%] vs one [1%]), and maculopapular rash (six [4%] vs none). Drug-related serious adverse events occurred in 12 (9%) patients in the regorafenib group and three (4%) in the placebo group. Interpretation This phase 3 trial is the second to show an overall survival benefit with regorafenib compared with placebo in patients with treatment-refractory metastatic colorectal cancer, substantiating the role of regorafenib as an important treatment option for patients whose disease has progressed after standard treatments. In this trial, preceding standard treatments did not necessarily include targeted treatments. Adverse events were generally consistent with the known safety profile of regorafenib in this setting. Funding Bayer HealthCare Pharmaceuticals.