Showing papers by "University of Chicago published in 2019"
The George Institute for Global Health1, Royal North Shore Hospital2, Concord Repatriation General Hospital3, Imperial College London4, University of Sydney5, New York University6, Harvard University7, Janssen Pharmaceutica8, Veterans Health Administration9, Indiana University – Purdue University Indianapolis10, University of Chicago11, Kolling Institute of Medical Research12, Utah System of Higher Education13, University of British Columbia14, University College London15, Peking University16, Lunenfeld-Tanenbaum Research Institute17, Stanford University18
TL;DR: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
Abstract: Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium...
3,233 citations
TL;DR: In this article, the Event Horizon Telescope was used to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87.
Abstract: When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, which is circular and encompasses a central depression in brightness with a flux ratio greater than or similar to 10: 1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 +/- 0.7) x 10(9) M-circle dot. Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.
2,589 citations
University of Pennsylvania1, University of Chicago2, University of Melbourne3, Emory University4, University of Cologne5, University of Kansas6, Medical University of Vienna7, Ohio State University8, University of California, San Francisco9, University of Texas MD Anderson Cancer Center10, Université de Montréal11, University of Minnesota12, McMaster University13, Royal Prince Alfred Hospital14, Karolinska Institutet15, University of Würzburg16, University of Michigan17, University of Oslo18, Novartis19, University of Lyon20
TL;DR: The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
Abstract: Background Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 ...
2,086 citations
TL;DR: It is suggested that the choice of convenient, seemingly effective proxies for ground truth can be an important source of algorithmic bias in many contexts.
Abstract: Health systems rely on commercial prediction algorithms to identify and help patients with complex health needs. We show that a widely used algorithm, typical of this industry-wide approach and affecting millions of patients, exhibits significant racial bias: At a given risk score, Black patients are considerably sicker than White patients, as evidenced by signs of uncontrolled illnesses. Remedying this disparity would increase the percentage of Black patients receiving additional help from 17.7 to 46.5%. The bias arises because the algorithm predicts health care costs rather than illness, but unequal access to care means that we spend less money caring for Black patients than for White patients. Thus, despite health care cost appearing to be an effective proxy for health by some measures of predictive accuracy, large racial biases arise. We suggest that the choice of convenient, seemingly effective proxies for ground truth can be an important source of algorithmic bias in many contexts.
2,003 citations
Tel Aviv University1, Katholieke Universiteit Leuven2, Fox Chase Cancer Center3, Sungkyunkwan University4, University College London5, Ruhr University Bochum6, Agostino Gemelli University Polyclinic7, Integra Telecom8, Technische Universität München9, Memorial Sloan Kettering Cancer Center10, AstraZeneca11, Merck & Co.12, University of Chicago13
TL;DR: Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo, and there was no significant between-group difference in health-related quality of life.
Abstract: Background Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate–ribose) polymerase (PARP) in...
1,321 citations
Broad Institute1, University of Chicago2, University of Geneva3, University of Dundee4, Columbia University5, Princeton University6, Max Planck Society7, Johns Hopkins University8, Stanford University9, Vanderbilt University10, University of Cambridge11, Vanderbilt University Medical Center12, Massachusetts Eye and Ear Infirmary13, Harvard University14, Scripps Health15, Polytechnic University of Catalonia16, University of Pennsylvania17
TL;DR: Analysis of the v8 data provides insights into the tissue-specificity of genetic effects, and shows that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.
Abstract: The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the v8 data, based on 17,382 RNA-sequencing samples from 54 tissues of 948 post-mortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue-specificity of genetic effects, and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.
1,243 citations
TL;DR: Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.
Abstract: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
1,090 citations
TL;DR: In this article, the authors present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign, and find that >50% of the total flux at arcsecond scales comes from near the horizon and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole.
Abstract: We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 ± 3 μas and constrain its fractional width to be <0.5. Associating the crescent feature with the emission surrounding the black hole shadow, we infer an angular gravitational radius of GM/Dc2 = 3.8 ± 0.4 μas. Folding in a distance measurement of ${16.8}_{-0.7}^{+0.8}\,\mathrm{Mpc}$ gives a black hole mass of $M=6.5\pm 0.2{| }_{\mathrm{stat}}\pm 0.7{| }_{\mathrm{sys}}\times {10}^{9}\hspace{2pt}{M}_{\odot }$. This measurement from lensed emission near the event horizon is consistent with the presence of a central Kerr black hole, as predicted by the general theory of relativity.
1,024 citations
TL;DR: The results suggest that an endogenous ‘lactate clock’ in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis, and represents an opportunity to improve the understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.
Abstract: The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.
968 citations
TL;DR: In this article, the first Event Horizon Telescope (EHT) images of M87 were presented, using observations from April 2017 at 1.3 mm wavelength, showing a prominent ring with a diameter of ~40 μas, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole.
Abstract: We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of ~40 μas, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.
952 citations
19 May 2019
TL;DR: This work presents the first robust and generalizable detection and mitigation system for DNN backdoor attacks, and identifies multiple mitigation techniques via input filters, neuron pruning and unlearning.
Abstract: Lack of transparency in deep neural networks (DNNs) make them susceptible to backdoor attacks, where hidden associations or triggers override normal classification to produce unexpected results. For example, a model with a backdoor always identifies a face as Bill Gates if a specific symbol is present in the input. Backdoors can stay hidden indefinitely until activated by an input, and present a serious security risk to many security or safety related applications, e.g. biometric authentication systems or self-driving cars. We present the first robust and generalizable detection and mitigation system for DNN backdoor attacks. Our techniques identify backdoors and reconstruct possible triggers. We identify multiple mitigation techniques via input filters, neuron pruning and unlearning. We demonstrate their efficacy via extensive experiments on a variety of DNNs, against two types of backdoor injection methods identified by prior work. Our techniques also prove robust against a number of variants of the backdoor attack.
TL;DR: It is shown that CeH9 can be synthesized at 80-100 GPa with laser heating, and is characterized by a clathrate structure with a dense 3-dimensional atomic hydrogen sublattice, which shed a significant light on the search for superhydrides in close similarity with atomic hydrogen within a feasible pressure range.
Abstract: Hydrogen-rich superhydrides are believed to be very promising high-Tc superconductors. Recent experiments discovered superhydrides at very high pressures, e.g. FeH5 at 130 GPa and LaH10 at 170 GPa. With the motivation of discovering new hydrogen-rich high-Tc superconductors at lowest possible pressure, here we report the prediction and experimental synthesis of cerium superhydride CeH9 at 80–100 GPa in the laser-heated diamond anvil cell coupled with synchrotron X-ray diffraction. Ab initio calculations were carried out to evaluate the detailed chemistry of the Ce-H system and to understand the structure, stability and superconductivity of CeH9. CeH9 crystallizes in a P63/mmc clathrate structure with a very dense 3-dimensional atomic hydrogen sublattice at 100 GPa. These findings shed a significant light on the search for superhydrides in close similarity with atomic hydrogen within a feasible pressure range. Discovery of superhydride CeH9 provides a practical platform to further investigate and understand conventional superconductivity in hydrogen rich superhydrides. Hydrogen-rich superhydrides are promising high-temperature superconductors which have been observed only at pressures above 170 GPa. Here the authors show that CeH9 can be synthesized at 80-100 GPa with laser heating, and is characterized by a clathrate structure with a dense 3-dimensional atomic hydrogen sublattice.
TL;DR: The Large Synoptic Survey Telescope (LSST) as discussed by the authors is a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachon in northern Chile.
Abstract: We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachon in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320–1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ~ 27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.
TL;DR: This review highlights recent progress in understanding the function of N6-methyladenosine (m6A), the most abundant internal mark on eukaryotic mRNA, in light of the specific biological contexts of m6A effectors, and emphasizes the importance of context for RNA modification regulation and function.
TL;DR: The current evidence for the role of abnormal placentation and therole of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia is discussed.
Abstract: Hypertensive disorders of pregnancy-chronic hypertension, gestational hypertension, and preeclampsia-are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.
University of Texas MD Anderson Cancer Center1, American College of Radiology2, University of Michigan3, University of Wisconsin Hospital and Clinics4, Cleveland Clinic5, University of California, San Francisco6, The Ohio State University Wexner Medical Center7, Yale University8, Fox Chase Cancer Center9, Princess Margaret Cancer Centre10, University Hospitals of Cleveland11, Ohio State University12, University of Oklahoma Health Sciences Center13, Stanford University14, Emory University15, University of Louisville16, Kaiser Permanente17, University of Alabama at Birmingham18, University of Chicago19
TL;DR: After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival, and patients were stratified by T category (T1-T2 vs T3-T4), N category (N0-N2a vs N2b-N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years).
TL;DR: The results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Abstract: Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
TL;DR: In this article, a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by GRS was constructed and compared with the observed visibilities.
Abstract: The Event Horizon Telescope (EHT) has mapped the central compact radio source of the elliptical galaxy M87 at 1.3 mm with unprecedented angular resolution. Here we consider the physical implications of the asymmetric ring seen in the 2017 EHT data. To this end, we construct a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by general relativistic ray tracing. We compare the observed visibilities with this library and confirm that the asymmetric ring is consistent with earlier predictions of strong gravitational lensing of synchrotron emission from a hot plasma orbiting near the black hole event horizon. The ring radius and ring asymmetry depend on black hole mass and spin, respectively, and both are therefore expected to be stable when observed in future EHT campaigns. Overall, the observed image is consistent with expectations for the shadow of a spinning Kerr black hole as predicted by general relativity. If the black hole spin and M87's large scale jet are aligned, then the black hole spin vector is pointed away from Earth. Models in our library of non-spinning black holes are inconsistent with the observations as they do not produce sufficiently powerful jets. At the same time, in those models that produce a sufficiently powerful jet, the latter is powered by extraction of black hole spin energy through mechanisms akin to the Blandford-Znajek process. We briefly consider alternatives to a black hole for the central compact object. Analysis of existing EHT polarization data and data taken simultaneously at other wavelengths will soon enable new tests of the GRMHD models, as will future EHT campaigns at 230 and 345 GHz.
TL;DR: In this article, the authors reported superconductivity with a critical temperature of around 250 kelvin within the [Formula: see text] structure of LaH10 at a pressure of about 170 gigapascals.
Abstract: With the discovery1 of superconductivity at 203 kelvin in H3S, attention returned to conventional superconductors with properties that can be described by the Bardeen-Cooper-Schrieffer and the Migdal-Eliashberg theories. Although these theories predict the possibility of room-temperature superconductivity in metals that have certain favourable properties-such as lattice vibrations at high frequencies-they are not sufficient to guide the design or predict the properties of new superconducting materials. First-principles calculations based on density functional theory have enabled such predictions, and have suggested a new family of superconducting hydrides that possess a clathrate-like structure in which the host atom (calcium, yttrium, lanthanum) is at the centre of a cage formed by hydrogen atoms2-4. For LaH10 and YH10, the onset of superconductivity is predicted to occur at critical temperatures between 240 and 320 kelvin at megabar pressures3-6. Here we report superconductivity with a critical temperature of around 250 kelvin within the [Formula: see text] structure of LaH10 at a pressure of about 170 gigapascals. This is, to our knowledge, the highest critical temperature that has been confirmed so far in a superconducting material. Superconductivity was evidenced by the observation of zero resistance, an isotope effect, and a decrease in critical temperature under an external magnetic field, which suggested an upper critical magnetic field of about 136 tesla at zero temperature. The increase of around 50 kelvin compared with the previous highest critical temperature1 is an encouraging step towards the goal of achieving room-temperature superconductivity in the near future.
TL;DR: The Event Horizon Telescope (EHT) as mentioned in this paper is a very long baseline interferometry (VLBI) array that comprises millimeter and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth.
Abstract: The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ~1.3 mm, EHT angular resolution (λ/D) is ~25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s^(−1), exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.
TL;DR: These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology.
Harvard University1, University of Chicago2, Columbia University3, University of Colorado Boulder4, Duke University5, Baptist Health6, Washington University in St. Louis7, University of Minnesota8, Houston Methodist Hospital9, University of Nebraska Medical Center10, Yale University11, MedStar Washington Hospital Center12, University of Michigan13, Advocate Lutheran General Hospital14, St Thomas' Hospital15, University of North Carolina at Chapel Hill16, Piedmont Hospital17, Abbott Laboratories18
TL;DR: Among patients with advanced heart failure, a fully magnetically levitated centrifugal‐flow left ventricular assist device was associated with less frequent need for pump replacement than an axial‐flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device.
Abstract: Background In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device ...
Stanford University1, University of Chicago2, Willamette University3, Wageningen University and Research Centre4, University of Bristol5, Bat Conservation International6, Stockholm Resilience Centre7, Royal Swedish Academy of Sciences8, Wellcome Trust9, University of Washington10, Uppsala University11, University of Illinois at Urbana–Champaign12, The Nature Conservancy13, Heidelberg University14, University of Glasgow15, Chinese Academy of Sciences16, University of Virginia17, University of British Columbia18, University of Exeter19
TL;DR: It is shown how ecosystem service assessments can be expanded to include mental health, and a heuristic, conceptual model for doing so is provided.
Abstract: A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.
TL;DR: The authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types to illustrate how common clinical problems are being addressed.
Abstract: Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.
TL;DR: In this paper, the authors improved initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data.
Abstract: On August 17, 2017, the Advanced LIGO and Advanced Virgo gravitational-wave detectors observed a low-mass compact binary inspiral. The initial sky localization of the source of the gravitational-wave signal, GW170817, allowed electromagnetic observatories to identify NGC 4993 as the host galaxy. In this work, we improve initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data. We extend the range of gravitational-wave frequencies considered down to 23 Hz, compared to 30 Hz in the initial analysis. We also compare results inferred using several signal models, which are more accurate and incorporate additional physical effects as compared to the initial analysis. We improve the localization of the gravitational-wave source to a 90% credible region of 16 deg2. We find tighter constraints on the masses, spins, and tidal parameters, and continue to find no evidence for nonzero component spins. The component masses are inferred to lie between 1.00 and 1.89 M when allowing for large component spins, and to lie between 1.16 and 1.60 M (with a total mass 2.73-0.01+0.04 M) when the spins are restricted to be within the range observed in Galactic binary neutron stars. Using a precessing model and allowing for large component spins, we constrain the dimensionless spins of the components to be less than 0.50 for the primary and 0.61 for the secondary. Under minimal assumptions about the nature of the compact objects, our constraints for the tidal deformability parameter Λ are (0,630) when we allow for large component spins, and 300-230+420 (using a 90% highest posterior density interval) when restricting the magnitude of the component spins, ruling out several equation-of-state models at the 90% credible level. Finally, with LIGO and GEO600 data, we use a Bayesian analysis to place upper limits on the amplitude and spectral energy density of a possible postmerger signal.
TL;DR: It is shown that deep residual learning can predict MSI directly from H&E histology, which is ubiquitously available and has the potential to provide immunotherapy to a much broader subset of patients with gastrointestinal cancer.
Abstract: Microsatellite instability determines whether patients with gastrointestinal cancer respond exceptionally well to immunotherapy. However, in clinical practice, not every patient is tested for MSI, because this requires additional genetic or immunohistochemical tests. Here we show that deep residual learning can predict MSI directly from H&E histology, which is ubiquitously available. This approach has the potential to provide immunotherapy to a much broader subset of patients with gastrointestinal cancer.
University of Pennsylvania1, University of Texas MD Anderson Cancer Center2, University of Marburg3, Memorial Sloan Kettering Cancer Center4, University of Bologna5, Carlos III Health Institute6, University of Maryland, Baltimore7, University of Chicago8, University of Minnesota9, University of Alabama at Birmingham10, Medical University of South Carolina11, University of California, San Francisco12, Thomas Jefferson University13, National Taiwan University14, Yale University15, Centre Hospitalier Universitaire de Toulouse16, University of Fukui17, Seoul National University18, University of Ulsan19, Wake Forest University20, Harvard University21, Astellas Pharma22, Johns Hopkins University23
TL;DR: Gilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML.
Abstract: Background Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemothera...
Cleveland Clinic1, Queen Mary University of London2, Georgetown University3, Institut Gustave Roussy4, Beth Israel Deaconess Medical Center5, Autonomous University of Barcelona6, University of Chicago7, Aarhus University Hospital8, University of Ulsan9, Ludwig Maximilian University of Munich10, Osaka University11, Palacký University, Olomouc12, Macquarie University13, University of Tübingen14, Harvard University15, Ashford University16, Hoffmann-La Roche17, Genentech18, Memorial Sloan Kettering Cancer Center19
TL;DR: Results of IMmotion151 support atezolizumab plus bevacIZumab as a first-line treatment option for selected patients with advanced renal cell carcinoma and showed a favourable safety profile.
TL;DR: In this paper, the Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5-11 observing campaign are presented.
Abstract: We present the calibration and reduction of Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5–11 observing campaign. These global very long baseline interferometric observations include for the first time the highly sensitive Atacama Large Millimeter/submillimeter Array (ALMA); reaching an angular resolution of 25 μas, with characteristic sensitivity limits of ~1 mJy on baselines to ALMA and ~10 mJy on other baselines. The observations present challenges for existing data processing tools, arising from the rapid atmospheric phase fluctuations, wide recording bandwidth, and highly heterogeneous array. In response, we developed three independent pipelines for phase calibration and fringe detection, each tailored to the specific needs of the EHT. The final data products include calibrated total intensity amplitude and phase information. They are validated through a series of quality assurance tests that show consistency across pipelines and set limits on baseline systematic errors of 2% in amplitude and 1° in phase. The M87 data reveal the presence of two nulls in correlated flux density at ~3.4 and ~8.3 Gλ and temporal evolution in closure quantities, indicating intrinsic variability of compact structure on a timescale of days, or several light-crossing times for a few billion solar-mass black hole. These measurements provide the first opportunity to image horizon-scale structure in M87.
University of Texas at Austin1, University of California, Irvine2, Stanford University3, Northwestern University4, Michigan State University5, University of Virginia6, University of Chicago7, Paradigm8, ICF International9, Arizona State University10, Pennsylvania State University11, Harvard University12, University of Pennsylvania13
TL;DR: A US national experiment showed that a short, online, self-administered growth mindset intervention can increase adolescents’ grades and advanced course-taking, and identified the types of school that were poised to benefit the most.
Abstract: A global priority for the behavioural sciences is to develop cost-effective, scalable interventions that could improve the academic outcomes of adolescents at a population level, but no such interventions have so far been evaluated in a population-generalizable sample. Here we show that a short (less than one hour), online growth mindset intervention-which teaches that intellectual abilities can be developed-improved grades among lower-achieving students and increased overall enrolment to advanced mathematics courses in a nationally representative sample of students in secondary education in the United States. Notably, the study identified school contexts that sustained the effects of the growth mindset intervention: the intervention changed grades when peer norms aligned with the messages of the intervention. Confidence in the conclusions of this study comes from independent data collection and processing, pre-registration of analyses, and corroboration of results by a blinded Bayesian analysis.