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Showing papers by "New York University published in 2015"


Journal ArticleDOI
28 May 2015-Nature
TL;DR: Deep learning is making major advances in solving problems that have resisted the best attempts of the artificial intelligence community for many years, and will have many more successes in the near future because it requires very little engineering by hand and can easily take advantage of increases in the amount of available computation and data.
Abstract: Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.

46,982 citations


Journal ArticleDOI
Mohsen Naghavi1, Haidong Wang1, Rafael Lozano1, Adrian Davis2  +728 moreInstitutions (294)
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.

5,792 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

5,668 citations


Journal ArticleDOI
TL;DR: This paper reviews the principles and practice of purposeful sampling in implementation research, summarizes types and categories of purposefully sampling strategies and provides a set of recommendations for use of single strategy or multistage strategy designs, particularly for state implementation research.
Abstract: Purposeful sampling is widely used in qualitative research for the identification and selection of information-rich cases related to the phenomenon of interest. Although there are several different purposeful sampling strategies, criterion sampling appears to be used most commonly in implementation research. However, combining sampling strategies may be more appropriate to the aims of implementation research and more consistent with recent developments in quantitative methods. This paper reviews the principles and practice of purposeful sampling in implementation research, summarizes types and categories of purposeful sampling strategies and provides a set of recommendations for use of single strategy or multistage strategy designs, particularly for state implementation research.

5,601 citations


Journal ArticleDOI
28 Aug 2015-Science
TL;DR: A large-scale assessment suggests that experimental reproducibility in psychology leaves a lot to be desired, and correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Abstract: Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.

5,532 citations


Journal ArticleDOI
21 May 2015-Cell
TL;DR: Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together.

5,506 citations


Journal ArticleDOI
Theo Vos1, Ryan M Barber1, Brad Bell1, Amelia Bertozzi-Villa1  +686 moreInstitutions (287)
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.

4,510 citations


01 May 2015
TL;DR: Drop-seq as discussed by the authors analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin, and identifies 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes.
Abstract: Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. VIDEO ABSTRACT.

3,365 citations


Journal ArticleDOI
TL;DR: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrogram, and a novel optical interferometer.
Abstract: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 sq. deg of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-Object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include measured abundances of 15 different elements for each star. In total, SDSS-III added 2350 sq. deg of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 sq. deg; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5,513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.

2,471 citations


Journal ArticleDOI
Christina Fitzmaurice1, Christina Fitzmaurice2, Daniel Dicker2, Daniel Dicker1, Amanda W Pain2, Hannah Hamavid2, Maziar Moradi-Lakeh2, Michael F. MacIntyre3, Michael F. MacIntyre2, Christine Allen2, Gillian M. Hansen2, Rachel Woodbrook2, Charles D.A. Wolfe2, Randah R. Hamadeh4, Ami R. Moore5, A. Werdecker6, Bradford D. Gessner, Braden Te Ao, Brian J. McMahon7, Chante Karimkhani8, Chuanhua Yu9, Graham S Cooke10, David C. Schwebel11, David O. Carpenter12, David M. Pereira13, Denis Nash, Dhruv S. Kazi14, Diego De Leo15, Dietrich Plass16, Kingsley N. Ukwaja17, George D. Thurston, Kim Yun Jin18, Edgar P. Simard19, Edward J Mills20, Eun-Kee Park21, Ferrán Catalá-López22, Gabrielle deVeber, Carolyn C. Gotay23, Gulfaraz Khan24, H. Dean Hosgood25, Itamar S. Santos26, Janet L Leasher27, Jasvinder A. Singh28, James Leigh12, Jost B. Jonas29, Juan R. Sanabria30, Justin Beardsley31, Justin Beardsley32, Kathryn H. Jacobsen33, Ken Takahashi34, Richard C. Franklin, Luca Ronfani35, Marcella Montico36, Luigi Naldi36, Marcello Tonelli, Johanna M. Geleijnse37, Max Petzold38, Mark G. Shrime39, Mark G. Shrime40, Mustafa Z. Younis41, Naohiro Yonemoto42, Nicholas J K Breitborde, Paul S. F. Yip43, Farshad Pourmalek44, Paulo A. Lotufo24, Alireza Esteghamati27, Graeme J. Hankey45, Raghib Ali46, Raimundas Lunevicius33, Reza Malekzadeh47, Robert P. Dellavalle45, Robert G. Weintraub48, Robert G. Weintraub49, Robyn M. Lucas50, Robyn M. Lucas51, Roderick J Hay52, David Rojas-Rueda, Ronny Westerman, Sadaf G. Sepanlou53, Sandra Nolte, Scott B. Patten54, Scott Weichenthal37, Semaw Ferede Abera55, Seyed-Mohammad Fereshtehnejad56, Ivy Shiue57, Tim Driscoll58, Tim Driscoll59, Tommi J. Vasankari29, Ubai Alsharif, Vafa Rahimi-Movaghar54, Vasiliy Victorovich Vlassov45, W. S. Marcenes60, Wubegzier Mekonnen61, Yohannes Adama Melaku62, Yuichiro Yano56, Al Artaman63, Ismael Campos, Jennifer H MacLachlan41, Ulrich O Mueller, Daniel Kim53, Matias Trillini64, Babak Eshrati65, Hywel C Williams66, Kenji Shibuya67, Rakhi Dandona68, Kinnari S. Murthy69, Benjamin C Cowie69, Azmeraw T. Amare, Carl Abelardo T. Antonio70, Carlos A Castañeda-Orjuela71, Coen H. Van Gool, Francesco Saverio Violante, In-Hwan Oh72, Kedede Deribe73, Kjetil Søreide62, Kjetil Søreide74, Luke D. Knibbs75, Luke D. Knibbs76, Maia Kereselidze77, Mark Green78, Rosario Cardenas79, Nobhojit Roy80, Taavi Tillmann57, Yongmei Li81, Hans Krueger82, Lorenzo Monasta24, Subhojit Dey36, Sara Sheikhbahaei, Nima Hafezi-Nejad45, G Anil Kumar45, Chandrashekhar T Sreeramareddy69, Lalit Dandona83, Haidong Wang2, Haidong Wang69, Stein Emil Vollset2, Ali Mokdad84, Ali Mokdad76, Joshua A. Salomon2, Rafael Lozano41, Theo Vos2, Mohammad H. Forouzanfar2, Alan D. Lopez2, Christopher J L Murray50, Mohsen Naghavi2 
University of Washington1, Institute for Health Metrics and Evaluation2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Cancer Treatment Centers of America31, Case Western Reserve University32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of the Witwatersrand39, University of Gothenburg40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, University of Colorado Denver48, Veterans Health Administration49, University of Melbourne50, Royal Children's Hospital51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, University of Edinburgh58, Northumbria University59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, Stavanger University Hospital75, University of Bergen76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

2,375 citations


Journal ArticleDOI
TL;DR: The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipILimumab monotherapy.
Abstract: BackgroundIn a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma. MethodsIn this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, we randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivolumab (1 mg per kilogram) or placebo once every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors. ResultsAmong patients with BRAF wild-type tumors, the rate of confirmed objective response was 61% (44 of 72 patients) in the group that received both ipilimumab and ni...

Journal ArticleDOI
11 Dec 2015-Science
TL;DR: A computational model is described that learns in a similar fashion and does so better than current deep learning algorithms and can generate new letters of the alphabet that look “right” as judged by Turing-like tests of the model's output in comparison to what real humans produce.
Abstract: People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms-for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world's alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches. We also present several "visual Turing tests" probing the model's creative generalization abilities, which in many cases are indistinguishable from human behavior.

Journal ArticleDOI
27 Nov 2015-Science
TL;DR: A key role is revealed for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade, which is found to depend on distinct Bacteroides species in mice and patients.
Abstract: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

Proceedings ArticleDOI
07 Dec 2015
TL;DR: This paper addresses three different computer vision tasks using a single basic architecture: depth prediction, surface normal estimation, and semantic labeling using a multiscale convolutional network that is able to adapt easily to each task using only small modifications.
Abstract: In this paper we address three different computer vision tasks using a single basic architecture: depth prediction, surface normal estimation, and semantic labeling. We use a multiscale convolutional network that is able to adapt easily to each task using only small modifications, regressing from the input image to the output map directly. Our method progressively refines predictions using a sequence of scales, and captures many image details without any superpixels or low-level segmentation. We achieve state-of-the-art performance on benchmarks for all three tasks.

Journal ArticleDOI
TL;DR: Current data on the clinical validity and utility of TILs in BC are reviewed in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections.

Posted Content
TL;DR: This article constructed several large-scale datasets to show that character-level convolutional networks could achieve state-of-the-art or competitive results in text classification.
Abstract: This article offers an empirical exploration on the use of character-level convolutional networks (ConvNets) for text classification. We constructed several large-scale datasets to show that character-level convolutional networks could achieve state-of-the-art or competitive results. Comparisons are offered against traditional models such as bag of words, n-grams and their TFIDF variants, and deep learning models such as word-based ConvNets and recurrent neural networks.

Proceedings Article
07 Dec 2015
TL;DR: A generative parametric model capable of producing high quality samples of natural images using a cascade of convolutional networks within a Laplacian pyramid framework to generate images in a coarse-to-fine fashion.
Abstract: In this paper we introduce a generative parametric model capable of producing high quality samples of natural images. Our approach uses a cascade of convolutional networks within a Laplacian pyramid framework to generate images in a coarse-to-fine fashion. At each level of the pyramid, a separate generative convnet model is trained using the Generative Adversarial Nets (GAN) approach [11]. Samples drawn from our model are of significantly higher quality than alternate approaches. In a quantitative assessment by human evaluators, our CIFAR10 samples were mistaken for real images around 40% of the time, compared to 10% for samples drawn from a GAN baseline model. We also show samples from models trained on the higher resolution images of the LSUN scene dataset.

Proceedings Article
07 Dec 2015
TL;DR: This paper proposed an end-to-end memory network with a recurrent attention model over a possibly large external memory, which can be seen as an extension of RNNsearch to the case where multiple computational steps (hops) are performed per output symbol.
Abstract: We introduce a neural network with a recurrent attention model over a possibly large external memory. The architecture is a form of Memory Network [23] but unlike the model in that work, it is trained end-to-end, and hence requires significantly less supervision during training, making it more generally applicable in realistic settings. It can also be seen as an extension of RNNsearch [2] to the case where multiple computational steps (hops) are performed per output symbol. The flexibility of the model allows us to apply it to tasks as diverse as (synthetic) question answering [22] and to language modeling. For the former our approach is competitive with Memory Networks, but with less supervision. For the latter, on the Penn TreeBank and Text8 datasets our approach demonstrates comparable performance to RNNs and LSTMs. In both cases we show that the key concept of multiple computational hops yields improved results.

Proceedings ArticleDOI
01 Jan 2015
TL;DR: A brief overview of the librosa library's functionality is provided, along with explanations of the design goals, software development practices, and notational conventions.
Abstract: This document describes version 0.4.0 of librosa: a Python pack- age for audio and music signal processing. At a high level, librosa provides implementations of a variety of common functions used throughout the field of music information retrieval. In this document, a brief overview of the library's functionality is provided, along with explanations of the design goals, software development practices, and notational conventions.

Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

Journal ArticleDOI
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +5117 moreInstitutions (314)
TL;DR: 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.
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.

Proceedings Article
06 Jul 2015
TL;DR: It is found that adding a bias of 1 to the LSTM's forget gate closes the gap between the L STM and the recently-introduced Gated Recurrent Unit (GRU) on some but not all tasks.
Abstract: The Recurrent Neural Network (RNN) is an extremely powerful sequence model that is often difficult to train. The Long Short-Term Memory (LSTM) is a specific RNN architecture whose design makes it much easier to train. While wildly successful in practice, the LSTM's architecture appears to be ad-hoc so it is not clear if it is optimal, and the significance of its individual components is unclear. In this work, we aim to determine whether the LSTM architecture is optimal or whether much better architectures exist. We conducted a thorough architecture search where we evaluated over ten thousand different RNN architectures, and identified an architecture that outperforms both the LSTM and the recently-introduced Gated Recurrent Unit (GRU) on some but not all tasks. We found that adding a bias of 1 to the LSTM's forget gate closes the gap between the LSTM and the GRU.

Journal ArticleDOI
TL;DR: In this article, the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma were compared.
Abstract: Summary Background Patients with melanoma that progresses on ipilimumab and, if BRAF V600 mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma. Methods We carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF V600 mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0–1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF V600 mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients. Findings Between Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0·57, 95% CI 0·45–0·73; p Interpretation These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma. Funding Merck Sharp & Dohme.


Posted Content
TL;DR: A neural network with a recurrent attention model over a possibly large external memory that is trained end-to-end, and hence requires significantly less supervision during training, making it more generally applicable in realistic settings.
Abstract: We introduce a neural network with a recurrent attention model over a possibly large external memory. The architecture is a form of Memory Network (Weston et al., 2015) but unlike the model in that work, it is trained end-to-end, and hence requires significantly less supervision during training, making it more generally applicable in realistic settings. It can also be seen as an extension of RNNsearch to the case where multiple computational steps (hops) are performed per output symbol. The flexibility of the model allows us to apply it to tasks as diverse as (synthetic) question answering and to language modeling. For the former our approach is competitive with Memory Networks, but with less supervision. For the latter, on the Penn TreeBank and Text8 datasets our approach demonstrates comparable performance to RNNs and LSTMs. In both cases we show that the key concept of multiple computational hops yields improved results.

Posted Content
TL;DR: In this paper, a multi-scale architecture, an adversarial training method, and an image gradient difference loss function were proposed to predict future frames from a video sequence. But their performance was not as good as those of the previous works.
Abstract: Learning to predict future images from a video sequence involves the construction of an internal representation that models the image evolution accurately, and therefore, to some degree, its content and dynamics. This is why pixel-space video prediction may be viewed as a promising avenue for unsupervised feature learning. In addition, while optical flow has been a very studied problem in computer vision for a long time, future frame prediction is rarely approached. Still, many vision applications could benefit from the knowledge of the next frames of videos, that does not require the complexity of tracking every pixel trajectories. In this work, we train a convolutional network to generate future frames given an input sequence. To deal with the inherently blurry predictions obtained from the standard Mean Squared Error (MSE) loss function, we propose three different and complementary feature learning strategies: a multi-scale architecture, an adversarial training method, and an image gradient difference loss function. We compare our predictions to different published results based on recurrent neural networks on the UCF101 dataset

Journal ArticleDOI
20 Feb 2015-Science
TL;DR: The two main approaches to creating stiff bonds, based on DNA-based materials synthesis, are reviewed, offering perhaps the most versatile way of organizing optically active materials into architectures that exhibit unusual and deliberately tailorable plasmonic and photonic properties.
Abstract: For over half a century, the biological roles of nucleic acids as catalytic enzymes, intracellular regulatory molecules, and the carriers of genetic information have been studied extensively. More recently, the sequence-specific binding properties of DNA have been exploited to direct the assembly of materials at the nanoscale. Integral to any methodology focused on assembling matter from smaller pieces is the idea that final structures have well-defined spacings, orientations, and stereo-relationships. This requirement can be met by using DNA-based constructs that present oriented nanoscale bonding elements from rigid core units. Here, we draw analogy between such building blocks and the familiar chemical concepts of "bonds" and "valency" and review two distinct but related strategies that have used this design principle in constructing new configurations of matter.

Journal ArticleDOI
TL;DR: Inhibition of glutaminolysis, the essential component of ferroptosis, can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases.

Journal ArticleDOI
TL;DR: The clearance systems of the brain as they relate to proteins implicated in AD pathology are described, with the main focus on Aβ.
Abstract: Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.