scispace - formally typeset
Browse all papers

Book ChapterDOI
08 Oct 2016-
Abstract: We consider image transformation problems, where an input image is transformed into an output image. Recent methods for such problems typically train feed-forward convolutional neural networks using a per-pixel loss between the output and ground-truth images. Parallel work has shown that high-quality images can be generated by defining and optimizing perceptual loss functions based on high-level features extracted from pretrained networks. We combine the benefits of both approaches, and propose the use of perceptual loss functions for training feed-forward networks for image transformation tasks. We show results on image style transfer, where a feed-forward network is trained to solve the optimization problem proposed by Gatys et al. in real-time. Compared to the optimization-based method, our network gives similar qualitative results but is three orders of magnitude faster. We also experiment with single-image super-resolution, where replacing a per-pixel loss with a perceptual loss gives visually pleasing results.

5,568 citations


Journal ArticleDOI
TL;DR: The latest version of STRING more than doubles the number of organisms it covers, and offers an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input.
Abstract: Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.

5,475 citations


Posted Content
TL;DR: YOLO9000, a state-of-the-art, real-time object detection system that can detect over 9000 object categories, is introduced and a method to jointly train on object detection and classification is proposed, both novel and drawn from prior work.
Abstract: We introduce YOLO9000, a state-of-the-art, real-time object detection system that can detect over 9000 object categories. First we propose various improvements to the YOLO detection method, both novel and drawn from prior work. The improved model, YOLOv2, is state-of-the-art on standard detection tasks like PASCAL VOC and COCO. At 67 FPS, YOLOv2 gets 76.8 mAP on VOC 2007. At 40 FPS, YOLOv2 gets 78.6 mAP, outperforming state-of-the-art methods like Faster RCNN with ResNet and SSD while still running significantly faster. Finally we propose a method to jointly train on object detection and classification. Using this method we train YOLO9000 simultaneously on the COCO detection dataset and the ImageNet classification dataset. Our joint training allows YOLO9000 to predict detections for object classes that don't have labelled detection data. We validate our approach on the ImageNet detection task. YOLO9000 gets 19.7 mAP on the ImageNet detection validation set despite only having detection data for 44 of the 200 classes. On the 156 classes not in COCO, YOLO9000 gets 16.0 mAP. But YOLO can detect more than just 200 classes; it predicts detections for more than 9000 different object categories. And it still runs in real-time.

5,470 citations


Posted Content
Abstract: Feature pyramids are a basic component in recognition systems for detecting objects at different scales. But recent deep learning object detectors have avoided pyramid representations, in part because they are compute and memory intensive. In this paper, we exploit the inherent multi-scale, pyramidal hierarchy of deep convolutional networks to construct feature pyramids with marginal extra cost. A top-down architecture with lateral connections is developed for building high-level semantic feature maps at all scales. This architecture, called a Feature Pyramid Network (FPN), shows significant improvement as a generic feature extractor in several applications. Using FPN in a basic Faster R-CNN system, our method achieves state-of-the-art single-model results on the COCO detection benchmark without bells and whistles, surpassing all existing single-model entries including those from the COCO 2016 challenge winners. In addition, our method can run at 5 FPS on a GPU and thus is a practical and accurate solution to multi-scale object detection. Code will be made publicly available.

5,416 citations


Journal ArticleDOI
TL;DR: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.
Abstract: BackgroundSomatic mutations have the potential to encode “non-self” immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. MethodsWe conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti–programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair–deficient colorectal cancers, patients with mismatch repair–proficient colorectal cancers, and patients with mismatch repair–deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. ResultsThe immune-related objective response rate and immune-related progression-free survival ...

5,399 citations


Journal ArticleDOI
13 Feb 2015-Science
TL;DR: An updated and extended analysis of the planetary boundary (PB) framework and identifies levels of anthropogenic perturbations below which the risk of destabilization of the Earth system (ES) is likely to remain low—a “safe operating space” for global societal development.
Abstract: The planetary boundaries framework defines a safe operating space for humanity based on the intrinsic biophysical processes that regulate the stability of the Earth system. Here, we revise and update the planetary boundary framework, with a focus on the underpinning biophysical science, based on targeted input from expert research communities and on more general scientific advances over the past 5 years. Several of the boundaries now have a two-tier approach, reflecting the importance of cross-scale interactions and the regional-level heterogeneity of the processes that underpin the boundaries. Two core boundaries—climate change and biosphere integrity—have been identified, each of which has the potential on its own to drive the Earth system into a new state should they be substantially and persistently transgressed.

5,367 citations


Posted Content
20 Jul 2017-arXiv: Learning
TL;DR: A new family of policy gradient methods for reinforcement learning, which alternate between sampling data through interaction with the environment, and optimizing a "surrogate" objective function using stochastic gradient ascent, are proposed.
Abstract: We propose a new family of policy gradient methods for reinforcement learning, which alternate between sampling data through interaction with the environment, and optimizing a "surrogate" objective function using stochastic gradient ascent. Whereas standard policy gradient methods perform one gradient update per data sample, we propose a novel objective function that enables multiple epochs of minibatch updates. The new methods, which we call proximal policy optimization (PPO), have some of the benefits of trust region policy optimization (TRPO), but they are much simpler to implement, more general, and have better sample complexity (empirically). Our experiments test PPO on a collection of benchmark tasks, including simulated robotic locomotion and Atari game playing, and we show that PPO outperforms other online policy gradient methods, and overall strikes a favorable balance between sample complexity, simplicity, and wall-time.

5,348 citations


Proceedings ArticleDOI
21 Jul 2017-
Abstract: We present a simple, highly modularized network architecture for image classification. Our network is constructed by repeating a building block that aggregates a set of transformations with the same topology. Our simple design results in a homogeneous, multi-branch architecture that has only a few hyper-parameters to set. This strategy exposes a new dimension, which we call cardinality (the size of the set of transformations), as an essential factor in addition to the dimensions of depth and width. On the ImageNet-1K dataset, we empirically show that even under the restricted condition of maintaining complexity, increasing cardinality is able to improve classification accuracy. Moreover, increasing cardinality is more effective than going deeper or wider when we increase the capacity. Our models, named ResNeXt, are the foundations of our entry to the ILSVRC 2016 classification task in which we secured 2nd place. We further investigate ResNeXt on an ImageNet-5K set and the COCO detection set, also showing better results than its ResNet counterpart. The code and models are publicly available online.

5,343 citations


Journal ArticleDOI
Abstract: BackgroundPembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non–small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). MethodsIn this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator’s choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. ResultsMedi...

5,332 citations


Proceedings ArticleDOI
13 Aug 2016-
Abstract: Prediction tasks over nodes and edges in networks require careful effort in engineering features used by learning algorithms. Recent research in the broader field of representation learning has led to significant progress in automating prediction by learning the features themselves. However, present feature learning approaches are not expressive enough to capture the diversity of connectivity patterns observed in networks. Here we propose node2vec, an algorithmic framework for learning continuous feature representations for nodes in networks. In node2vec, we learn a mapping of nodes to a low-dimensional space of features that maximizes the likelihood of preserving network neighborhoods of nodes. We define a flexible notion of a node's network neighborhood and design a biased random walk procedure, which efficiently explores diverse neighborhoods. Our algorithm generalizes prior work which is based on rigid notions of network neighborhoods, and we argue that the added flexibility in exploring neighborhoods is the key to learning richer representations. We demonstrate the efficacy of node2vec over existing state-of-the-art techniques on multi-label classification and link prediction in several real-world networks from diverse domains. Taken together, our work represents a new way for efficiently learning state-of-the-art task-independent representations in complex networks.

5,295 citations


Journal ArticleDOI
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
Abstract: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1–negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1–negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)

5,279 citations


Proceedings ArticleDOI
Mark Sandler1, Andrew Howard1, Menglong Zhu1, Andrey Zhmoginov1, Liang-Chieh Chen1 
18 Jun 2018-
Abstract: In this paper we describe a new mobile architecture, MobileNetV2, that improves the state of the art performance of mobile models on multiple tasks and benchmarks as well as across a spectrum of different model sizes. We also describe efficient ways of applying these mobile models to object detection in a novel framework we call SSDLite. Additionally, we demonstrate how to build mobile semantic segmentation models through a reduced form of DeepLabv3 which we call Mobile DeepLabv3. is based on an inverted residual structure where the shortcut connections are between the thin bottleneck layers. The intermediate expansion layer uses lightweight depthwise convolutions to filter features as a source of non-linearity. Additionally, we find that it is important to remove non-linearities in the narrow layers in order to maintain representational power. We demonstrate that this improves performance and provide an intuition that led to this design. Finally, our approach allows decoupling of the input/output domains from the expressiveness of the transformation, which provides a convenient framework for further analysis. We measure our performance on ImageNet [1] classification, COCO object detection [2], VOC image segmentation [3]. We evaluate the trade-offs between accuracy, and number of operations measured by multiply-adds (MAdd), as well as actual latency, and the number of parameters.

5,263 citations


Book
25 Dec 2021-
Abstract: The aim of interpretative phenomenological analysis (IPA) is to explore in detail how participants are making sense of their personal and social world, and the main currency for an IPA study is the meanings particular experiences, events, states hold for participants. The approach is phenomenological (see Chapter 3) in that it involves detailed examination of the participant’s lifeworld; it attempts to explore personal experience and is concerned with an individual’s personal perception or account of an object or event, as opposed to an attempt to produce an objective statement of the object or event itself. At the same time, IPA also emphasizes that the research exercise is a dynamic process with an active role for the researcher in that process. One is trying to get close to the participant’s personal world, to take, in Conrad’s (1987) words, an ‘insider’s perspective’, but one cannot do this directly or completely. Access depends on, and is complicated by, the researcher’s own conceptions; indeed, these are required in order to make sense of that other personal world through a process of interpretative activity. Thus, a two-stage interpretation process, or a double hermeneutic, is involved. The participants are trying to make sense of their world; the researcher is trying to make sense of the participants trying to make sense of their world. IPA is therefore intellectually connected to hermeneutics and theories of interpretation (Packer and Addison, 1989; Palmer, 1969; Smith, in press; see also Chapter 2 this volume). Different interpretative stances are possible, and IPA combines an empathic hermeneutics with a questioning hermeneutics. Thus, consistent with its phenomenological origins, IPA is concerned with trying to understand what it is like, from the point of view of the participants, to take their side. At the same time, a detailed IPA analysis can also involve asking critical questions of the texts from participants, such as the following: What is the person trying to achieve here? Is something leaking out here that wasn’t intended? Do I have a sense of something going on here that maybe the participants themselves are less aware of?

5,211 citations


Book
30 Nov 2021-
Abstract: In this work Tim Ingold offers a persuasive new approach to understanding how human beings perceive their surroundings. He argues that what we are used to calling cultural variation consists, in the first place, of variations in skill. Neither innate nor acquired, skills are grown, incorporated into the human organism through practice and training in an environment. They are thus as much biological as cultural. To account for the generation of skills we have therefore to understand the dynamics of development. And this in turn calls for an ecological approach that situates practitioners in the context of an active engagement with the constituents of their surroundings. The twenty-three essays comprising this book focus in turn on the procurement of livelihood, on what it means to ‘dwell’, and on the nature of skill, weaving together approaches from social anthropology, ecological psychology, developmental biology and phenomenology in a way that has never been attempted before. The book is set to revolutionise the way we think about what is ‘biological’ and ‘cultural’ in humans, about evolution and history, and indeed about what it means for human beings – at once organisms and persons – to inhabit an environment. The Perception of the Environment will be essential reading not only for anthropologists but also for biologists, psychologists, archaeologists, geographers and philosophers.

5,210 citations


Proceedings ArticleDOI
François Chollet1
21 Jul 2017-
TL;DR: This work proposes a novel deep convolutional neural network architecture inspired by Inception, where Inception modules have been replaced with depthwise separable convolutions, and shows that this architecture, dubbed Xception, slightly outperforms Inception V3 on the ImageNet dataset, and significantly outperforms it on a larger image classification dataset.
Abstract: We present an interpretation of Inception modules in convolutional neural networks as being an intermediate step in-between regular convolution and the depthwise separable convolution operation (a depthwise convolution followed by a pointwise convolution). In this light, a depthwise separable convolution can be understood as an Inception module with a maximally large number of towers. This observation leads us to propose a novel deep convolutional neural network architecture inspired by Inception, where Inception modules have been replaced with depthwise separable convolutions. We show that this architecture, dubbed Xception, slightly outperforms Inception V3 on the ImageNet dataset (which Inception V3 was designed for), and significantly outperforms Inception V3 on a larger image classification dataset comprising 350 million images and 17,000 classes. Since the Xception architecture has the same number of parameters as Inception V3, the performance gains are not due to increased capacity but rather to a more efficient use of model parameters.

5,200 citations


Journal ArticleDOI
13 Mar 2020-Science
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

5,197 citations


Proceedings Article
19 Jun 2016-
TL;DR: A conceptually simple and lightweight framework for deep reinforcement learning that uses asynchronous gradient descent for optimization of deep neural network controllers and shows that asynchronous actor-critic succeeds on a wide variety of continuous motor control problems as well as on a new task of navigating random 3D mazes using a visual input.
Abstract: We propose a conceptually simple and lightweight framework for deep reinforcement learning that uses asynchronous gradient descent for optimization of deep neural network controllers. We present asynchronous variants of four standard reinforcement learning algorithms and show that parallel actor-learners have a stabilizing effect on training allowing all four methods to successfully train neural network controllers. The best performing method, an asynchronous variant of actor-critic, surpasses the current state-of-the-art on the Atari domain while training for half the time on a single multi-core CPU instead of a GPU. Furthermore, we show that asynchronous actor-critic succeeds on a wide variety of continuous motor control problems as well as on a new task of navigating random 3D mazes using a visual input.

5,192 citations


Proceedings ArticleDOI
12 Aug 2016-
TL;DR: This paper introduces a simpler and more effective approach, making the NMT model capable of open-vocabulary translation by encoding rare and unknown words as sequences of subword units, and empirically shows that subword models improve over a back-off dictionary baseline for the WMT 15 translation tasks English-German and English-Russian by 1.3 BLEU.
Abstract: Neural machine translation (NMT) models typically operate with a fixed vocabulary, but translation is an open-vocabulary problem. Previous work addresses the translation of out-of-vocabulary words by backing off to a dictionary. In this paper, we introduce a simpler and more effective approach, making the NMT model capable of open-vocabulary translation by encoding rare and unknown words as sequences of subword units. This is based on the intuition that various word classes are translatable via smaller units than words, for instance names (via character copying or transliteration), compounds (via compositional translation), and cognates and loanwords (via phonological and morphological transformations). We discuss the suitability of different word segmentation techniques, including simple character ngram models and a segmentation based on the byte pair encoding compression algorithm, and empirically show that subword models improve over a back-off dictionary baseline for the WMT 15 translation tasks English!German and English!Russian by up to 1.1 and 1.3 BLEU, respectively.

5,164 citations


Proceedings ArticleDOI
21 Jul 2017-
Abstract: Despite the breakthroughs in accuracy and speed of single image super-resolution using faster and deeper convolutional neural networks, one central problem remains largely unsolved: how do we recover the finer texture details when we super-resolve at large upscaling factors? The behavior of optimization-based super-resolution methods is principally driven by the choice of the objective function. Recent work has largely focused on minimizing the mean squared reconstruction error. The resulting estimates have high peak signal-to-noise ratios, but they are often lacking high-frequency details and are perceptually unsatisfying in the sense that they fail to match the fidelity expected at the higher resolution. In this paper, we present SRGAN, a generative adversarial network (GAN) for image super-resolution (SR). To our knowledge, it is the first framework capable of inferring photo-realistic natural images for 4x upscaling factors. To achieve this, we propose a perceptual loss function which consists of an adversarial loss and a content loss. The adversarial loss pushes our solution to the natural image manifold using a discriminator network that is trained to differentiate between the super-resolved images and original photo-realistic images. In addition, we use a content loss motivated by perceptual similarity instead of similarity in pixel space. Our deep residual network is able to recover photo-realistic textures from heavily downsampled images on public benchmarks. An extensive mean-opinion-score (MOS) test shows hugely significant gains in perceptual quality using SRGAN. The MOS scores obtained with SRGAN are closer to those of the original high-resolution images than to those obtained with any state-of-the-art method.

5,157 citations


Proceedings Article
06 Jul 2015-
TL;DR: An attention based model that automatically learns to describe the content of images is introduced that can be trained in a deterministic manner using standard backpropagation techniques and stochastically by maximizing a variational lower bound.
Abstract: Inspired by recent work in machine translation and object detection, we introduce an attention based model that automatically learns to describe the content of images. We describe how we can train this model in a deterministic manner using standard backpropagation techniques and stochastically by maximizing a variational lower bound. We also show through visualization how the model is able to automatically learn to fix its gaze on salient objects while generating the corresponding words in the output sequence. We validate the use of attention with state-of-the-art performance on three benchmark datasets: Flickr9k, Flickr30k and MS COCO.

5,142 citations


Journal ArticleDOI
26 May 2020-JAMA
TL;DR: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area and assesses outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death.
Abstract: Importance There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

5,140 citations


Journal ArticleDOI
03 Apr 2015-Science
TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
Abstract: Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.

5,020 citations



Journal ArticleDOI
Mohsen Naghavi1, Haidong Wang1, Rafael Lozano1, Adrian Davis2, Xiaofeng Liang3, Maigeng Zhou, Stein Emil Vollset4, Stein Emil Vollset5, Stein Emil Vollset1, Ayse Abbasoglu Ozgoren6, Safa Abdalla, Foad Abd-Allah7, M A Aziz, Semaw Ferede Abera8, Victor Aboyans, Biju Abraham9, Jerry Puthenpurakal Abraham10, Katrina Abuabara11, Ibrahim Abubakar2, Laith J. Abu-Raddad12, Niveen M E Abu-Rmeileh, Tom Achoki1, Ademola Lukman Adelekan, Zanfina Ademi13, Koranteng Adofo14, Arsène Kouablan Adou, Jose C. Adsuar15, Johan Ärnlöv16, Emilie Agardh, Dickens Akena17, Mazin J. Al Khabouri, Deena Alasfoor, Mohammed I. Albittar, Miguel Angel Alegretti18, Alicia Aleman18, Zewdie Aderaw Alemu19, Rafael Alfonso-Cristancho1, Samia Alhabib20, Mohammed K. Ali21, Raghib Ali22, François Alla23, Faris Al Lami24, Peter Allebeck, Mohammad A. AlMazroa, Rustam Al-Shahi Salman25, Ubai Alsharif26, Elena Alvarez, Nelson Alviz-Guzman27, Adansi A. Amankwaa28, Azmeraw T. Amare29, Omid Ameli30, Hassan Amini31, Walid Ammar, H. Ross Anderson32, Benjamin O. Anderson1, Carl Abelardo T. Antonio33, Palwasha Anwari34, Henry Apfel1, Solveig A. Cunningham21, Valentina Arsić Arsenijević35, Al Artaman36, Majed Asad, Rana J. Asghar, Reza Assadi37, Lydia S. Atkins, Charles Atkinson1, Alaa Badawi38, Maria Cecilia Bahit, Talal Bakfalouni, Kalpana Balakrishnan39, Shivanthi Balalla40, Amitava Banerjee41, Ryan M Barber1, Suzanne Barker-Collo, Simón Barquera, Lars Barregard42, Lope H Barrero43, Tonatiuh Barrientos-Gutiérrez, Arindam Basu44, Sanjay Basu45, Mohammed Basulaiman, Justin Beardsley22, Neeraj Bedi, Ettore Beghi46, Tolesa Bekele, Michelle L. Bell47, Corina Benjet, Derrick A Bennett22, Isabela M. Benseñor, Habib Benzian48, Amelia Bertozzi-Villa1, Tariku Jibat Beyene49, Neeraj Bhala, Ashish Bhalla50, Zulfiqar A Bhutta, Boris Bikbov51, Aref A. Bin Abdulhak52, Stan Biryukov1, Jed D. Blore13, Fiona M. Blyth53, Megan Bohensky13, Guilherme Borges, Dipan Bose54, Soufiane Boufous, Rupert R A Bourne55, Lindsay N. Boyers56, Michael Brainin57, Michael Brauer58, Carol Brayne59, Alexandra Brazinova60, Nicholas J K Breitborde61, Hermann Brenner62, Adam D M Briggs22, J Brown1, Traolach S. Brugha63, Geoffrey Buckle64, Linh N Bui65, Gene Bukhman66, Michael Burch48, Ismael Ricardo Campos Nonato, Hélène Carabin67, Rosario Cárdenas68, Jonathan R. Carapetis69, David O. Carpenter70, Valeria Caso71, Carlos A Castañeda-Orjuela, Ruben Castro72, Ferrán Catalá-López, Fiorella Cavalleri18, Jung-Chen Chang73, Jung-Chen Chang74, Fiona C. Charlson75, Xuan Che76, Honglei Chen76, Yingyao Chen77, Jian Sheng Chen, Zhengming Chen22, Peggy Pei-Chia Chiang, Odgerel Chimed-Ochir78, Rajiv Chowdhury59, Hanne Christensen79, Costas A. Christophi80, Ting Wu Chuang, Sumeet S. Chugh81, Massimo Cirillo82, Matthew M Coates1, Luc E. Coffeng1, Megan Coggeshall1, Aaron Cohen83, Valentina Colistro18, Samantha M. Colquhoun13, Mercedes Colomar, Leslie T. Cooper84, Cyrus Cooper85, Luis M. Coppola, Monica Cortinovis46, Karen J. Courville86, Benjamin C Cowie, Michael H. Criqui87, John A. Crump88, Lucía Cuevas-Nasu, Iuri da Costa Leite89, Kaustubh Dabhadkar21, Lalit Dandona90, Lalit Dandona1, Rakhi Dandona90, Emily Dansereau1, Paul I. Dargan91, Anand Dayama92, Vanessa De la Cruz-Góngora, Shelley F. De La Vega93, Diego De Leo94, Louisa Degenhardt95, Borja del Pozo-Cruz96, Robert P. Dellavalle, Kebede Deribe49, Don C. Des Jarlais97, Muluken Dessalegn, Gabrielle de Veber98, Samath D Dharmaratne99, Mukesh Dherani100, José Luis Díaz-Ortega, Cesar Diaz-Torne101, Daniel Dicker1, Eric L. Ding66, Klara Dokova102, E. Ray Dorsey103, Tim Driscoll53, Leilei Duan, Herbert C. Duber1, Adnan M. Durrani76, Beth E. Ebel1, Karen Edmond104, Richard G. Ellenbogen1, Yousef M. Elshrek105, Sergey Petrovich Ermakov106, Holly E. Erskine75, Babak Eshrati107, Alireza Esteghamati, Kara Estep1, Thomas Fürst, Saman Fahimi66, Anna S. Fahrion108, Emerito Jose A. Faraon33, Farshad Farzadfar109, Derek F J Fay2, Andrea B. Feigl66, Valery L. Feigin40, Manuela Mendonca Felicio, Seyed-Mohammad Fereshtehnejad, Jefferson G Fernandes, Alize J. Ferrari75, Thomas D. Fleming1, Nataliya Foigt110, Kyle J Foreman111, Mohammad H. Forouzanfar1, F. Gerry R. Fowkes25, Urbano Fra Paleo15, Richard C. Franklin112, Neal D. Futran1, Lynne Gaffikin45, Ketevan Gambashidze113, Fortuné Gbètoho Gankpé, Francisco A García-Guerra, Ana C. Garcia, Johanna M. Geleijnse114, Bradford D. Gessner, Katherine B Gibney115, Richard F. Gillum116, Stuart Gilmour117, Ibrahim Abdelmageem Mohamed Ginawi, Maurice Giroud118, Elizabeth Glaser119, Shifalika Goenka90, Héctor Gómez Dantés, Philimon Gona64, Diego Gonzalez-Medina1, Caterina Guinovart, Rashmi Gupta, Rajeev Gupta, Richard A. Gosselin120, Carolyn C. Gotay58, Atsushi Goto, Hebe N. Gouda75, Nicholas Graetz1, K. Fern Greenwell1, Harish Chander Gugnani121, David Gunnell122, Reyna A Gutiérrez, Juanita A. Haagsma1, Nima Hafezi-Nejad, Holly Hagan123, Maria Hagströmer124, Yara A. Halasa119, Randah R. Hamadeh125, Hannah Hamavid1, Mouhanad Hammami126, Jamie Hancock1, Graeme J. Hankey104, Gillian M. Hansen1, Hilda L Harb, Heather Harewood, Josep Maria Haro127, Rasmus Havmoeller124, Roderick J. Hay, Simon I. Hay22, Mohammad Taghi Hedayati128, Ileana B. Heredia Pi, Kyle R. Heuton1, Pouria Heydarpour109, Hideki Higashi1, Martha Híjar, Hans W. Hoek, Howard J. Hoffman76, John Hornberger, H. Dean Hosgood97, Mazeda Hossain129, Peter J. Hotez130, Damian G Hoy75, Damian G Hoy131, Mohamed Hsairi, Guoqing Hu132, John J Huang47, Mark D. Huffman133, Andrew J. Hughes, Abdullatif Husseini134, Chantal Huynh1, Marissa Iannarone1, Kim Moesgaard Iburg135, Bulat Idrisov119, Nayu Ikeda, Kaire Innos76, Manami Inoue, Farhad Islami136, Samaya Ismayilova, Kathryn H. Jacobsen137, Simerjot K. Jassal87, Simerjot K. Jassal138, Sudha Jayaraman139, Paul N. Jensen1, Vivekanand Jha50, Guohong Jiang, Ying Jiang78, Jost B. Jonas140, Jonathan C. Joseph1, Knud Juel141, Edmond K. Kabagambe142, Haidong Kan77, André Karch, Chante Karimkhani143, Ganesan Karthikeyan144, Nicholas J Kassebaum1, Anil Kaul145, Norito Kawakami, Konstantin Kazanjan113, Dhruv S. Kazi120, Andrew H. Kemp, Andre Pascal Kengne146, Andre Keren147, Maia Kereselidze113, Yousef Khader148, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmad Khan149, Gulfaraz Khan150, Young-Ho Khang151, Christian Kieling152, Yohannes Kinfu153, Jonas Minet Kinge, Daniel Kim154, Sungroul Kim155, Miia Kivipelto, Luke D. Knibbs75, Ann Kristin Knudsen4, Yoshihiro Kokubo, Sowarta Kosen, Meera Kotagal1, Michael Kravchenko156, Sanjay Krishnaswami157, Hans Krueger, Barthelemy Kuate Defo158, Ernst J. Kuipers, Burcu Kucuk Bicer6, Chanda Kulkarni, Veena S. Kulkarni159, Kaushalendra Kumar160, Ravi Kumar, Gene F. Kwan30, Hmwe H Kyu1, Taavi Lai, Arjun Lakshmana Balaji13, Ratilal Lalloo161, Tea Lallukka162, Tea Lallukka163, Hilton Lam93, Qing Lan76, Van C. Lansingh, Heidi J. Larson129, Anders Larsson16, Pablo M. Lavados164, Alicia Elena Beatriz Lawrynowicz, Janet L Leasher165, Jongmin Lee166, James Leigh53, Mall Leinsalu76, Ricky Leung70, Carly E Levitz1, Bin Li167, Yichong Li, Yongmei Li168, Chelsea A. Liddell1, Stephen S Lim86, Graça Maria Ferreira De Lima, Maggie Lind1, Steven E. Lipshultz169, Shiwei Liu, Yang Liu21, Belinda K Lloyd170, Belinda K Lloyd115, Katherine T. Lofgren1, Giancarlo Logroscino171, Stephanie J. London76, Joannie Lortet-Tieulent136, Paulo A. Lotufo172, Robyn M. Lucas173, Raimundas Lunevicius100, Ronan A Lyons174, Stefan Ma175, Vasco Manuel Pedro Machado, Michael F. MacIntyre1, Mark T Mackay176, Jennifer H MacLachlan, Carlos Magis-Rodriguez, Abbas Ali Mahdi177, Marek Majdan60, Reza Malekzadeh109, Srikanth Mangalam, Christopher C. Mapoma178, Marape Marape130, Wagner Marcenes179, Christopher Margono1, Guy B. Marks180, Melvin Barrientos Marzan181, Joseph R. Masci, Mohammad T Mashal182, Felix Masiye178, Amanda J. Mason-Jones183, Richard Matzopolous146, Bongani M. Mayosi184, Tasara T. Mazorodze, John J. McGrath75, Abigail C. McKay, Martin McKee129, Abigail McLain1, Peter A. Meaney11, Man Mohan Mehndiratta, Fabiola Mejía-Rodríguez, Yohannes Adama Melaku8, Michele Meltzer185, Ziad A. Memish, Walter Mendoza34, George A. Mensah76, Atte Meretoja13, Francis Apolinary Mhimbira186, Ted R. Miller187, Ted R. Miller188, Edward J Mills189, Awoke Misganaw189, Santosh Mishra, Charles Mock1, Terrie E. Moffitt190, Norlinah Mohamed Ibrahim191, Karzan Abdulmuhsin Mohammad, Ali H. Mokdad1, Glen Mola192, Lorenzo Monasta, Jonathan de la Cruz Monis, Julio Cesar Montañez Hernandez, Marcella Montico, Thomas J. Montine1, Meghan D. Mooney1, Ami R. Moore193, Maziar Moradi-Lakeh1, Andrew E. Moran143, Rintaro Mori, Joanna Moschandreas194, Wilkister N. Moturi195, Madeline L. Moyer1, Dariush Mozaffarian196, Ulrich O Mueller197, Mitsuru Mukaigawara198, Erin C Mullany1, Joseph Murray59, Adetoun Mustapha199, Paria Naghavi1, Aliya Naheed200, Kovin Naidoo201, Luigi Naldi, Devina Nand, Vinay Nangia, K.M. Venkat Narayan21, Denis Nash202, Jamal Nasher, Chakib Nejjari203, Robert G. Nelson76, Marian L. Neuhouser204, Sudan Prasad Neupane205, Polly A. Newcomb204, Lori M. Newman108, C. R. Newton108, Marie Ng1, Frida Namnyak Ngalesoni206, Grant Nguyen1, Nhung T Nguyen65, Muhammad Imran Nisar207, Sandra Nolte26, Ole Frithjof Norheim5, Rosana E. Norman75, Bo Norrving208, Luke Nyakarahuka17, Shaun Odell1, Martin O'Donnell209, Takayoshi Ohkubo210, Summer Lockett Ohno1, Bolajoko O. Olusanya, Saad B. Omer21, John Nelson Opio, Orish Ebere Orisakwe211, Katrina F Ortblad1, Alberto Ortiz212, Maria Lourdes K. Otayza213, Amanda W Pain1, Jeyaraj D Pandian214, Carlo Irwin A. Panelo33, Jeemon Panniyammakal, Christina Papachristou26, Angel J Paternina Caicedo27, Scott B. Patten215, George C Patton13, Vinod K. Paul144, Boris I. Pavlin, Neil Pearce129, Carlos A. Pellegrini1, David M. Pereira216, Sophie C. Peresson217, Rogelio Pérez-Padilla, Fernando Perez-Ruiz, Norberto Perico46, Aslam Pervaiz, Konrad Pesudovs218, Carrie Beth Peterson219, Max Petzold42, Bryan K. Phillips1, David Phillips1, Michael R. Phillips21, Michael R. Phillips220, Dietrich Plass221, Frédéric B. Piel22, Dan Poenaru222, Suzanne Polinder, Svetlana Popova98, Richie Poulton88, Farshad Pourmalek58, Dorairaj Prabhakaran, Dima M. Qato, Amado D Quezada, D. Alex Quistberg1, Felicia A. Rabito223, Anwar Rafay, Kazem Rahimi22, Vafa Rahimi-Movaghar109, Sajjad Ur Rahman224, Murugesan Raju225, Ivo Rakovac108, Saleem M Rana226, Saleem M Rana227, Amany H Refaat228, Giuseppe Remuzzi46, Antonio Luiz Pinho Ribeiro229, Stefano Ricci, Patricia M. Riccio230, Lee Richardson1, Jan Hendrik Richardus231, Bayard Roberts129, D. Allen Roberts1, Margaret Robinson1, Anna Roca, Alina Rodriguez111, David Rojas-Rueda, Luca Ronfani, Robin Room170, Gregory A. Roth1, Dietrich Rothenbacher232, David H. Rothstein233, Jane Rowley, Nobhojit Roy234, George Mugambage Ruhago235, Lesley Rushton111, Sankar Sambandam39, Kjetil Søreide236, Mohammad Yahya Saeedi, Sukanta Saha75, Ramesh Sahathevan237, Mohammad Ali Sahraian109, Berhe W. Sahle8, Joshua A. Salomon66, Deborah Salvo, Genesis May J. Samonte, Uchechukwu K.A. Sampson142, Juan Sanabria238, Logan Sandar1, Itamar S. Santos172, Maheswar Satpathy95, Monika Sawhney239, Mete Saylan240, Peter Scarborough22, Ben Schöttker62, Jürgen C Schmidt2, Ione Jayce Ceola Schneider241, Austin E Schumacher1, David C. Schwebel242, James Scott75, Sadaf G. Sepanlou109, Edson Serván-Mori, Katya Anne Shackelford1, Amira Shaheen243, Saeid Shahraz119, Marina Shakh-Nazarova113, Siyi Shangguan66, Jun She77, Sara Sheikhbahaei, Donald S. Shepard119, Kenji Shibuya117, Yukito Shinohara, Kawkab Shishani244, Ivy Shiue245, Rupak Shivakoti243, Mark G. Shrime66, Inga Dora Sigfusdottir246, Donald H. Silberberg11, Andrea P. Silva, Edgar P. Simard21, Shireen Sindi124, Jasvinder A. Singh242, Lavanya Singh1, Edgar Sioson1, Vegard Skirbekk, Karen Sliwa, Samuel So, Michael Soljak111, Samir Soneji247, Sergey Soshnikov, Luciano A. Sposato230, Chandrashekhar T Sreeramareddy248, Jeffrey D. Stanaway1, Vasiliki Stathopoulou, Kyle Steenland21, Claudia Stein, Caitlyn Steiner1, Antony Stevens1, Heidi Stöckl129, Kurt Straif249, Konstantinos Stroumpoulis, Lela Sturua113, Bruno F. Sunguya235, Soumya Swaminathan, Mamta Swaroop133, Bryan L. Sykes250, Karen M. Tabb251, Ken Takahashi78, Roberto Tchio Talongwa, Feng Tan252, David Tanne253, Marcel Tanner254, Marcel Tanner255, Mohammad Tavakkoli256, Braden Te Ao40, Carolina Maria Teixeira, Tara Templin1, Eric Y. Tenkorang257, Abdullah Sulieman Terkawi258, Bernadette Thomas1, Andrew L. Thorne-Lyman259, Amanda G. Thrift115, George D. Thurston123, Taavi Tillmann129, David L. Tirschwell1, Imad M. Tleyjeh84, Imad M. Tleyjeh260, Marcello Tonelli261, Fotis Topouzis262, Jeffrey A. Towbin263, Hideaki Toyoshima, Jefferson Traebert, Bach Xuan Tran264, Thomas Truelsen79, Ulises Trujillo, Matias Trillini46, Zacharie Tsala Dimbuene265, Miltiadis K. Tsilimbaris, E. Murat Tuzcu266, Clotilde Ubeda, Uche S. Uchendu267, Kingsley N. Ukwaja, Eduardo A. Undurraga119, Andrew Vallely95, Steven van de Vijver, Coen H. Van Gool, Yuri Y Varakin156, Tommi Vasankari, Ana Maria Nogales Vasconcelos268, Monica S. Vavilala1, Narayanaswamy Venketasubramanian, Lakshmi Vijayakumar, Salvador Villalpando, Francesco Saverio Violante269, Vasiliy Victorovich Vlassov270, Gregory R. Wagner271, Stephen G. Waller272, JianLi Wang215, Linhong Wang, Xiao Rong Wang273, Yanping Wang, Tati S. Warouw, Scott Weichenthal274, Elisabete Weiderpass, Robert G. Weintraub13, Robert G. Weintraub176, Wang Wenzhi275, Andrea Werdecker, K. Ryan Wessells276, Ronny Westerman197, Harvey Whiteford75, James D. Wilkinson277, Thomas N. Williams111, Solomon Meseret Woldeyohannes278, Charles D.A. Wolfe279, Timothy M. Wolock1, Anthony D. Woolf, John Q. Wong, Jonathan L. Wright1, Sarah Wulf1, Brittany Wurtz1, Gelin Xu280, Yang Yang281, Yuichiro Yano282, Hiroshi Yatsuya283, Paul S. F. Yip284, Naohiro Yonemoto, Seok Jun Yoon166, Mustafa Z. Younis285, Chuanhua Yu286, Kim Yun Jin, Maysaa El Sayed Zaki287, Mohammed Fouad Zamakhshary, Hajo Zeeb288, Yong Zhang, Yong Zhao289, Yingfeng Zheng290, Jun Zhu, Shankuan Zhu291, David Zonies, Xiao Nong Zou292, Joseph R. Zunt1, Theo Vos1, Alan D. Lopez1, Alan D. Lopez13, Christopher J L Murray1, Gabriel Alcalá-Cerra, Howard Hu98, Nadim E. Karam293, Nsanzimana Sabin, A. M. Temesgen294 
University of Washington1, Public Health England2, Centers for Disease Control and Prevention3, Norwegian Institute of Public Health4, University of Bergen5, Hacettepe University6, Cairo University7, Mekelle University8, Metropolitan University9, University of Texas Health Science Center at San Antonio10, University of Pennsylvania11, Cornell University12, University of Melbourne13, Kwame Nkrumah University of Science and Technology14, University of Extremadura15, Uppsala University16, Makerere University17, University of the Republic18, Debre markos University19, National Guard Health Affairs20, Emory University21, University of Oxford22, University of Lorraine23, University of Baghdad24, University of Edinburgh25, Charité26, University of Cartagena27, Albany State University28, University of Groningen29, Boston University30, Kurdistan University of Medical Sciences31, St George's, University of London32, University of the Philippines Manila33, United Nations Population Fund34, University of Belgrade35, Pharmaceutical Product Development36, Mashhad University of Medical Sciences37, Public Health Agency of Canada38, Sri Ramachandra University39, Auckland University of Technology40, University of Birmingham41, University of Gothenburg42, Pontifical Xavierian University43, University of Canterbury44, Stanford University45, Mario Negri Institute for Pharmacological Research46, Yale University47, University College London48, Addis Ababa University49, Post Graduate Institute of Medical Education and Research50, Moscow State University of Medicine and Dentistry51, University of Missouri–Kansas City52, University of Sydney53, World Bank54, Anglia Ruskin University55, Georgetown University56, Danube University Krems57, University of British Columbia58, University of Cambridge59, University of Trnava60, University of Arizona61, German Cancer Research Center62, University of Leicester63, University of Massachusetts Medical School64, Hanoi School Of Public Health65, Harvard University66, University of Oklahoma67, Universidad Autónoma Metropolitana68, Telethon Institute for Child Health Research69, University at Albany, SUNY70, University of Perugia71, Diego Portales University72, Taipei Medical University73, National Taiwan University74, University of Queensland75, National Institutes of Health76, Fudan University77, University of Occupational and Environmental Health Japan78, University of Copenhagen79, Cyprus University of Technology80, Cedars-Sinai Medical Center81, University of Salerno82, Health Effects Institute83, Mayo Clinic84, University of Southampton85, Institute for Health Metrics and Evaluation86, University of California, San Diego87, University of Otago88, Oswaldo Cruz Foundation89, Public Health Foundation of India90, Guy's and St Thomas' NHS Foundation Trust91, Jacobi Medical Center92, University of the Philippines93, Griffith University94, University of New South Wales95, University of Auckland96, Yeshiva University97, University of Toronto98, University of Peradeniya99, University of Liverpool100, Autonomous University of Barcelona101, Medical University of Varna102, University of Rochester103, University of Western Australia104, University of Tripoli105, Russian Academy of Sciences106, Arak University of Medical Sciences107, World Health Organization108, Tehran University of Medical Sciences109, Academy of Medical Sciences, United Kingdom110, Imperial College London111, James Cook University112, National Center for Disease Control and Public Health113, Wageningen University and Research Centre114, Monash University115, Howard University116, University of Tokyo117, University of Burgundy118, Brandeis University119, University of California, San Francisco120, Saint James School of Medicine121, University of Bristol122, New York University123, Karolinska Institutet124, Arabian Gulf University125, Dallas County126, University of Barcelona127, Mazandaran University of Medical Sciences128, University of London129, Baylor College of Medicine130, Secretariat of the Pacific Community131, Central South University132, Northwestern University133, Qatar University134, Aarhus University135, American Cancer Society136, George Mason University137, Veterans Health Administration138, Virginia Commonwealth University139, Heidelberg University140, University of Southern Denmark141, Vanderbilt University142, Columbia University143, All India Institute of Medical Sciences144, Oklahoma State University–Stillwater145, South African Medical Research Council146, Hebrew University of Jerusalem147, Jordan University of Science and Technology148, Health Services Academy149, United Arab Emirates University150, Seoul National University151, Universidade Federal do Rio Grande do Sul152, University of Canberra153, Northeastern University154, Soonchunhyang University155, Russian Academy156, Oregon Health & Science University157, Université de Montréal158, Arkansas State University159, International Institute for Population Sciences160, University of Adelaide161, University of Helsinki162, Finnish Institute of Occupational Health163, Universidad del Desarrollo164, Nova Southeastern University165, Korea University166, Shandong University167, Genentech168, Wayne State University169, Box Hill Hospital170, University of Bari171, University of São Paulo172, Australian National University173, Swansea University174, Singapore Ministry of Health175, Royal Children's Hospital176, King George's Medical University177, University of Zambia178, Queen Mary University of London179, Woolcock Institute of Medical Research180, University of the East181, Democratic Republic of the Congo Ministry of Health182, University of York183, University of Cape Town184, Thomas Jefferson University185, Ifakara Health Institute186, Curtin University187, Pacific Institute188, University of Ottawa189, Duke University190, National University of Malaysia191, University of Papua New Guinea192, University of North Texas193, University of Crete194, Egerton University195, Tufts University196, University of Marburg197, Tokyo Medical and Dental University198, Medical Research Council199, International Centre for Diarrhoeal Disease Research, Bangladesh200, University of KwaZulu-Natal201, City University of New York202, Mohammed V University203, Fred Hutchinson Cancer Research Center204, University of Oslo205, Ministry of Health and Social Welfare206, Aga Khan University207, Lund University208, National University of Ireland, Galway209, Teikyo University210, University of Port Harcourt211, Autonomous University of Madrid212, Memorial Hospital of South Bend213, Christian Medical College & Hospital214, University of Calgary215, University of Porto216, International Diabetes Federation217, Flinders University218, Aalborg University219, Shanghai Jiao Tong University220, Environment Agency221, McMaster University222, Tulane University223, Hamad Medical Corporation224, University of Missouri225, Panjab University, Chandigarh226, University of the Punjab227, Walden University228, Universidade Federal de Minas Gerais229, University of Western Ontario230, Erasmus University Rotterdam231, University of Ulm232, Children's Memorial Hospital233, Bhabha Atomic Research Centre234, Muhimbili University of Health and Allied Sciences235, Stavanger University Hospital236, University Kebangsaan Malaysia Medical Centre237, Case Western Reserve University238, Marshall University239, Novartis240, Universidade Federal de Santa Catarina241, University of Alabama at Birmingham242, An-Najah National University243, Washington State University Spokane244, Heriot-Watt University245, Reykjavík University246, Dartmouth College247, Universiti Tunku Abdul Rahman248, International Agency for Research on Cancer249, University of California, Irvine250, University of Illinois at Chicago251, National Institute of Occupational Health252, Tel Aviv University253, University of Basel254, Swiss Tropical and Public Health Institute255, Westchester Medical Center256, Memorial University of Newfoundland257, University of Virginia258, WorldFish259, Alfaisal University260, University of Alberta261, Aristotle University of Thessaloniki262, Cincinnati Children's Hospital Medical Center263, Johns Hopkins University264, University of Kinshasa265, Cleveland Clinic266, United States Department of Veterans Affairs267, University of Brasília268, University of Bologna269, National Research University – Higher School of Economics270, National Institute for Occupational Safety and Health271, Uniformed Services University of the Health Sciences272, Chinese Center for Disease Control and Prevention273, Health Canada274, Capital Medical University275, University of California, Davis276, University of Miami277, University of Gondar278, King's College London279, Nanjing University280, University of North Carolina at Chapel Hill281, Jichi Medical University282, Fujita Health University283, University of Hong Kong284, Jackson State University285, Wuhan University286, Mansoura University287, Leibniz Association288, Chongqing Medical University289, Sun Yat-sen University290, Zhejiang University291, Peking Union Medical College292, University of Balamand293, Jhpiego294
10 Jan 2015-The Lancet
Abstract: Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

5,001 citations


17


Journal ArticleDOI
16 Apr 2020-Cell
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Abstract: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

4,968 citations


Journal ArticleDOI
TL;DR: The process of conducting a thematic analysis is illustrated through the presentation of an auditable decision trail, guiding interpreting and representing textual data and exploring issues of rigor and trustworthiness.
Abstract: As qualitative research becomes increasingly recognized and valued, it is imperative that it is conducted in a rigorous and methodical manner to yield meaningful and useful results. To be accepted ...

4,958 citations


Journal ArticleDOI
TL;DR: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population and for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors.
Abstract: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

4,942 citations


Journal ArticleDOI
12 Jun 2015-Science
TL;DR: An approach for depositing high-quality FAPbI3 films, involving FAP bI3 crystallization by the direct intramolecular exchange of dimethylsulfoxide (DMSO) molecules intercalated in PbI2 with formamidinium iodide is reported.
Abstract: The band gap of formamidinium lead iodide (FAPbI3) perovskites allows broader absorption of the solar spectrum relative to conventional methylammonium lead iodide (MAPbI3). Because the optoelectronic properties of perovskite films are closely related to film quality, deposition of dense and uniform films is crucial for fabricating high-performance perovskite solar cells (PSCs). We report an approach for depositing high-quality FAPbI3 films, involving FAPbI3 crystallization by the direct intramolecular exchange of dimethylsulfoxide (DMSO) molecules intercalated in PbI2 with formamidinium iodide. This process produces FAPbI3 films with (111)-preferred crystallographic orientation, large-grained dense microstructures, and flat surfaces without residual PbI2. Using films prepared by this technique, we fabricated FAPbI3-based PSCs with maximum power conversion efficiency greater than 20%.

4,891 citations


Proceedings Article
07 Dec 2015-
TL;DR: This work introduces a new learnable module, the Spatial Transformer, which explicitly allows the spatial manipulation of data within the network, and can be inserted into existing convolutional architectures, giving neural networks the ability to actively spatially transform feature maps.
Abstract: Convolutional Neural Networks define an exceptionally powerful class of models, but are still limited by the lack of ability to be spatially invariant to the input data in a computationally and parameter efficient manner. In this work we introduce a new learnable module, the Spatial Transformer, which explicitly allows the spatial manipulation of data within the network. This differentiable module can be inserted into existing convolutional architectures, giving neural networks the ability to actively spatially transform feature maps, conditional on the feature map itself, without any extra training supervision or modification to the optimisation process. We show that the use of spatial transformers results in models which learn invariance to translation, scale, rotation and more generic warping, resulting in state-of-the-art performance on several benchmarks, and for a number of classes of transformations.

4,869 citations


Book
08 Sep 2020-
TL;DR: A review of the comparative database from across the behavioral sciences suggests both that there is substantial variability in experimental results across populations and that WEIRD subjects are particularly unusual compared with the rest of the species – frequent outliers.
Abstract: Behavioral scientists routinely publish broad claims about human psychology and behavior in the world's top journals based on samples drawn entirely from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. Researchers - often implicitly - assume that either there is little variation across human populations, or that these "standard subjects" are as representative of the species as any other population. Are these assumptions justified? Here, our review of the comparative database from across the behavioral sciences suggests both that there is substantial variability in experimental results across populations and that WEIRD subjects are particularly unusual compared with the rest of the species - frequent outliers. The domains reviewed include visual perception, fairness, cooperation, spatial reasoning, categorization and inferential induction, moral reasoning, reasoning styles, self-concepts and related motivations, and the heritability of IQ. The findings suggest that members of WEIRD societies, including young children, are among the least representative populations one could find for generalizing about humans. Many of these findings involve domains that are associated with fundamental aspects of psychology, motivation, and behavior - hence, there are no obvious a priori grounds for claiming that a particular behavioral phenomenon is universal based on sampling from a single subpopulation. Overall, these empirical patterns suggests that we need to be less cavalier in addressing questions of human nature on the basis of data drawn from this particularly thin, and rather unusual, slice of humanity. We close by proposing ways to structurally re-organize the behavioral sciences to best tackle these challenges.

4,860 citations