Showing papers by "Ohio State University published in 2019"
European Bioinformatics Institute1, University of California, Santa Cruz2, University of Lausanne3, University of Bern4, Broad Institute5, Massachusetts Institute of Technology6, Yale University7, Brunel University London8, University of Warsaw9, Ohio State University10, Pompeu Fabra University11, King's College London12
TL;DR: This work generates primary data, creates bioinformatics tools and provides analysis to support the work of expert manual gene annotators and automated gene annotation pipelines to identify and characterise gene loci to the highest standard.
Abstract: The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.
2,095 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, University of Würzburg15, Karolinska Institutet16, 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
Roswell Park Cancer Institute1, Johns Hopkins University2, Duke University3, Brigham and Women's Hospital4, Mayo Clinic5, City of Hope National Medical Center6, Memorial Sloan Kettering Cancer Center7, Fred Hutchinson Cancer Research Center8, Fox Chase Cancer Center9, Yale Cancer Center10, Washington University in St. Louis11, University of California, San Diego12, University of Wisconsin-Madison13, University Hospitals of Cleveland14, University of Alabama at Birmingham15, Vanderbilt University16, Moffitt Cancer Center17, University of Colorado Boulder18, University of Tennessee Health Science Center19, University of California, San Francisco20, Northwestern University21, Ohio State University22, University of Michigan23, Stanford University24, University of Utah25, National Comprehensive Cancer Network26
TL;DR: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer.
Abstract: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
1,218 citations
Hospital Universitario La Paz1, Memorial Sloan Kettering Cancer Center2, Gynecologic Oncology Group3, Medical University of South Carolina4, Rigshospitalet5, McGill University Health Centre6, Ohio State University7, Thomas Jefferson University8, Medical College of Wisconsin9, Technion – Israel Institute of Technology10, GlaxoSmithKline11, University of Arizona12, University of Girona13, University of Pennsylvania14, Vita-Salute San Raffaele University15
TL;DR: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival thanThose who received placebo, regardless of the presence or absence of homologous-recombination deficiency.
Abstract: Background Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients ...
1,106 citations
University of New South Wales1, Oregon State University2, Braunschweig University of Technology3, University of California, San Diego4, Norwegian University of Life Sciences5, University of Liverpool6, Max Planck Society7, University of Tasmania8, University of Vermont9, ETH Zurich10, Stazione Zoologica Anton Dohrn11, Montana State University12, University of Amsterdam13, University of Southern California14, Pacific Northwest National Laboratory15, University of Hawaii at Manoa16, University of California, Berkeley17, Marine Biological Laboratory18, University of California, Irvine19, University of Georgia20, California Institute of Technology21, University of Edinburgh22, Ohio State University23, University of Sydney24, University of Alberta25, Georgia Institute of Technology26, University of Melbourne27, Australian Institute of Marine Science28, University of Texas Medical Branch29, University of Queensland30
TL;DR: This Consensus Statement documents the central role and global importance of microorganisms in climate change biology and puts humanity on notice that the impact of climate change will depend heavily on responses of micro organisms, which are essential for achieving an environmentally sustainable future.
Abstract: In the Anthropocene, in which we now live, climate change is impacting most life on Earth. Microorganisms support the existence of all higher trophic life forms. To understand how humans and other life forms on Earth (including those we are yet to discover) can withstand anthropogenic climate change, it is vital to incorporate knowledge of the microbial 'unseen majority'. We must learn not just how microorganisms affect climate change (including production and consumption of greenhouse gases) but also how they will be affected by climate change and other human activities. This Consensus Statement documents the central role and global importance of microorganisms in climate change biology. It also puts humanity on notice that the impact of climate change will depend heavily on responses of microorganisms, which are essential for achieving an environmentally sustainable future.
963 citations
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.
921 citations
University of Vermont1, Karolinska University Hospital2, Universidade Federal de Minas Gerais3, Universidade Católica de Pelotas4, University of Tokyo5, Fujita Health University6, Central University of Venezuela7, University of Trieste8, University of Cape Town9, Monash University10, Ohio State University11, University of Alberta12, Hospital General de México13, University of Waterloo14, American Society for Parenteral and Enteral Nutrition15, Brigham and Women's Hospital16, Saint Louis University Hospital17, Sapienza University of Rome18, La Trobe University19, Khon Kaen University20, HAN University of Applied Sciences21, Rabin Medical Center22, University of Illinois at Chicago23, Pontifical Catholic University of Chile24, University of São Paulo25, Peking Union Medical College Hospital26, University of Pennsylvania27, Free University of Brussels28
TL;DR: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed and it is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes.
Abstract: Summary Rationale This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings Methods In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications Results A two-step approach for the malnutrition diagnosis was selected, ie, first screening to identify “at risk” status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment Potential criteria were subjected to a ballot among the GLIM core and supporting working group members The top five ranked criteria included three phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden) To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories Conclusion A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback The diagnostic construct should be re-considered every 3–5 years
885 citations
TL;DR: The authors explore the potential of the 16S gene for discriminating bacterial taxa and show that full-length sequencing combined with appropriate clustering of intragenomic sequence variation can provide accurate representation of bacterial species in microbiome datasets.
Abstract: The 16S rRNA gene has been a mainstay of sequence-based bacterial analysis for decades. However, high-throughput sequencing of the full gene has only recently become a realistic prospect. Here, we use in silico and sequence-based experiments to critically re-evaluate the potential of the 16S gene to provide taxonomic resolution at species and strain level. We demonstrate that targeting of 16S variable regions with short-read sequencing platforms cannot achieve the taxonomic resolution afforded by sequencing the entire (~1500 bp) gene. We further demonstrate that full-length sequencing platforms are sufficiently accurate to resolve subtle nucleotide substitutions (but not insertions/deletions) that exist between intragenomic copies of the 16S gene. In consequence, we argue that modern analysis approaches must necessarily account for intragenomic variation between 16S gene copies. In particular, we demonstrate that appropriate treatment of full-length 16S intragenomic copy variants has the potential to provide taxonomic resolution of bacterial communities at species and strain level.
859 citations
Uppsala University1, Karolinska University Hospital2, University of Vermont3, Universidade Federal de Minas Gerais4, Universidade Católica de Pelotas5, University of Tokyo6, Fujita Health University7, Central University of Venezuela8, University of Trieste9, University of Cape Town10, University of Warwick11, Monash University12, Ohio State University13, University of Alberta14, Hospital General de México15, University of Waterloo16, American Society for Parenteral and Enteral Nutrition17, Brigham and Women's Hospital18, Saint Louis University Hospital19, Sapienza University of Rome20, Khon Kaen University21, VU University Amsterdam22, HAN University of Applied Sciences23, Rabin Medical Center24, Tel Aviv University25, University of Illinois at Chicago26, Pontifical Catholic University of Chile27, University of São Paulo28, Peking Union Medical College Hospital29, Free University of Brussels30, University of Pennsylvania31
TL;DR: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings.
Abstract: Rationale
This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings.
827 citations
TL;DR: This work shows how classical theory and modern practice can be reconciled within a single unified performance curve and proposes a mechanism underlying its emergence, and provides evidence for the existence and ubiquity of double descent for a wide spectrum of models and datasets.
Abstract: Breakthroughs in machine learning are rapidly changing science and society, yet our fundamental understanding of this technology has lagged far behind. Indeed, one of the central tenets of the field, the bias-variance trade-off, appears to be at odds with the observed behavior of methods used in modern machine-learning practice. The bias-variance trade-off implies that a model should balance underfitting and overfitting: Rich enough to express underlying structure in data and simple enough to avoid fitting spurious patterns. However, in modern practice, very rich models such as neural networks are trained to exactly fit (i.e., interpolate) the data. Classically, such models would be considered overfitted, and yet they often obtain high accuracy on test data. This apparent contradiction has raised questions about the mathematical foundations of machine learning and their relevance to practitioners. In this paper, we reconcile the classical understanding and the modern practice within a unified performance curve. This "double-descent" curve subsumes the textbook U-shaped bias-variance trade-off curve by showing how increasing model capacity beyond the point of interpolation results in improved performance. We provide evidence for the existence and ubiquity of double descent for a wide spectrum of models and datasets, and we posit a mechanism for its emergence. This connection between the performance and the structure of machine-learning models delineates the limits of classical analyses and has implications for both the theory and the practice of machine learning.
826 citations
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: There is an urgent need for research that examines how people actually move their faces to express emotions and other social information in the variety of contexts that make up everyday life, as well as careful study of the mechanisms by which people perceive instances of emotion in one another.
Abstract: It is commonly assumed that a person’s emotional state can be readily inferred from his or her facial movements, typically called emotional expressions or facial expressions. This assumption influences legal judgments, policy decisions, national security protocols, and educational practices; guides the diagnosis and treatment of psychiatric illness, as well as the development of commercial applications; and pervades everyday social interactions as well as research in other scientific fields such as artificial intelligence, neuroscience, and computer vision. In this article, we survey examples of this widespread assumption, which we refer to as the common view, and we then examine the scientific evidence that tests this view, focusing on the six most popular emotion categories used by consumers of emotion research: anger, disgust, fear, happiness, sadness, and surprise. The available scientific evidence suggests that people do sometimes smile when happy, frown when sad, scowl when angry, and so on, as proposed by the common view, more than what would be expected by chance. Yet how people communicate anger, disgust, fear, happiness, sadness, and surprise varies substantially across cultures, situations, and even across people within a single situation. Furthermore, similar configurations of facial movements variably express instances of more than one emotion category. In fact, a given configuration of facial movements, such as a scowl, often communicates something other than an emotional state. Scientists agree that facial movements convey a range of information and are important for social communication, emotional or otherwise. But our review suggests an urgent need for research that examines how people actually move their faces to express emotions and other social information in the variety of contexts that make up everyday life, as well as careful study of the mechanisms by which people perceive instances of emotion in one another. We make specific research recommendations that will yield a more valid picture of how people move their faces to express emotions and how they infer emotional meaning from facial movements in situations of everyday life. This research is crucial to provide consumers of emotion research with the translational information they require.
University of Texas MD Anderson Cancer Center1, Duke University2, Northwestern University3, City of Hope National Medical Center4, University of California, San Francisco5, Fox Chase Cancer Center6, Brigham and Women's Hospital7, University of California, San Diego8, Fred Hutchinson Cancer Research Center9, Memorial Sloan Kettering Cancer Center10, Vanderbilt University11, University of Utah12, University of Michigan13, Roswell Park Cancer Institute14, Mayo Clinic15, Yale Cancer Center16, Johns Hopkins University17, University of Colorado Boulder18, University of Wisconsin-Madison19, University Hospitals of Cleveland20, Washington University in St. Louis21, Ohio State University22, University of South Florida23, Stanford University24, University of Pennsylvania25, Harvard University26, National Comprehensive Cancer Network27
TL;DR: This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
Abstract: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
Seattle Cancer Care Alliance1, Memorial Sloan Kettering Cancer Center2, Duke University3, University of Wisconsin-Madison4, Brigham and Women's Hospital5, University of Michigan6, University of South Florida7, Fox Chase Cancer Center8, Harvard University9, Ohio State University10, Vanderbilt University11, Yale Cancer Center12, Stanford University13, University of Texas MD Anderson Cancer Center14, University of Colorado Boulder15, Roswell Park Cancer Institute16, University of Utah17, City of Hope National Medical Center18, University of Alabama at Birmingham19, Northwestern University20, Mayo Clinic21, Washington University in St. Louis22, Case Western Reserve University23, Johns Hopkins University24, University of Nebraska Medical Center25, University of Tennessee Health Science Center26, University of California, San Francisco27, University of California, San Diego28, National Comprehensive Cancer Network29
TL;DR: This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations.
Abstract: Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
Stanford University1, University of North Carolina at Chapel Hill2, Fred Hutchinson Cancer Research Center3, Vanderbilt University4, Anschutz Medical Campus5, University of Southern California6, Icahn School of Medicine at Mount Sinai7, University of California, San Francisco8, University of Hawaii9, University of Washington10, University of Texas Health Science Center at Houston11, University of Potsdam12, Johns Hopkins University13, Pennsylvania State University14, National Institutes of Health15, University of California, Davis16, Ohio State University17, Cancer Prevention Institute of California18, University of Vermont19, Rutgers University20
TL;DR: The value of diverse, multi-ethnic participants in large-scale genomic studies is demonstrated and evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications are shown.
Abstract: Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.
Vanderbilt University Medical Center1, Ohio State University2, The Ohio State University Wexner Medical Center3, Sutter Health4, University of California, San Francisco5, Stanford University6, VA Palo Alto Healthcare System7, Innovative Solutions & Support8, University of North Carolina at Chapel Hill9, Tufts Medical Center10, University of Chicago11, Houston Methodist Hospital12, Society of Critical Care Medicine13, Novant Health14, Saint Joseph Mercy Health System15, University of Pennsylvania16, Johns Hopkins University17
TL;DR: ABCDEF bundle performance showed significant and clinically meaningful improvements in outcomes including survival, mechanical ventilation use, coma, delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition.
Abstract: Objective:Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care.Design:Prospective, multicenter, cohort st
Lawrence Livermore National Laboratory1, University of Rochester2, Rutherford Appleton Laboratory3, École Polytechnique4, Ohio State University5, University of Michigan6, University of Jena7, Russian Academy of Sciences8, Osaka University9, Academy of Sciences of the Czech Republic10, Chinese Academy of Sciences11, Shanghai Jiao Tong University12, Gwangju Institute of Science and Technology13, Colorado State University14, University of Szeged15
TL;DR: In this paper, the authors provide a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed, and what technologies are to be deployed to get to these new regimes, and some critical issues facing their development.
Abstract: In the 2015 review paper 'Petawatt Class Lasers Worldwide' a comprehensive overview of the current status of highpower facilities of >200 TW was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multidisciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
TL;DR: This data-driven approach does not require numerical modeling of the imaging process or the estimation of a point-spread-function, and is based on training a generative adversarial network to transform diffraction-limited input images into super-resolved ones, and could serve to democratize super-resolution imaging.
Abstract: We present deep-learning-enabled super-resolution across different fluorescence microscopy modalities. This data-driven approach does not require numerical modeling of the imaging process or the estimation of a point-spread-function, and is based on training a generative adversarial network (GAN) to transform diffraction-limited input images into super-resolved ones. Using this framework, we improve the resolution of wide-field images acquired with low-numerical-aperture objectives, matching the resolution that is acquired using high-numerical-aperture objectives. We also demonstrate cross-modality super-resolution, transforming confocal microscopy images to match the resolution acquired with a stimulated emission depletion (STED) microscope. We further demonstrate that total internal reflection fluorescence (TIRF) microscopy images of subcellular structures within cells and tissues can be transformed to match the results obtained with a TIRF-based structured illumination microscope. The deep network rapidly outputs these super-resolved images, without any iterations or parameter search, and could serve to democratize super-resolution imaging.
Chinese Academy of Sciences1, University of California, Los Angeles2, University of Gothenburg3, Ohio State University4, University of Maryland, College Park5, Fudan University6, University of California, Santa Barbara7, Peking University8, Japan Agency for Marine-Earth Science and Technology9, University of Tsukuba10, Nanjing University11, San Diego State University12, University of Twente13, National Center for Atmospheric Research14, Texas A&M University15, Pacific Northwest National Laboratory16, Chengdu University of Information Technology17
TL;DR: The Third Pole (TP) is experiencing rapid warming and is currently in its warmest period in the past 2,000 years as mentioned in this paper, and the latest development in multidisciplinary TP research is reviewed in this paper.
Abstract: The Third Pole (TP) is experiencing rapid warming and is currently in its warmest period in the past 2,000 years. This paper reviews the latest development in multidisciplinary TP research ...
TL;DR: In this paper, a double-blind, controlled trial was conducted to evaluate the effect of caplacizumab on platelet normalization and recurrence of TTP.
Abstract: BACKGROUND
In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets.
METHODS
In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers.
RESULTS
The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period.
CONCLUSIONS
Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).
TL;DR: The DESI Legacy Imaging Surveys (http://legacysurvey.org/) as mentioned in this paper is a combination of three public projects (the Dark Energy Camera Legacy Survey, the Beijing-Arizona Sky Survey, and the Mayall z-band Legacy Survey) that will jointly image ≈14,000 deg2 of the extragalactic sky visible from the northern hemisphere in three optical bands (g, r, and z) using telescopes at the Kitt Peak National Observatory and the Cerro Tololo Inter-American Observatory.
Abstract: The DESI Legacy Imaging Surveys (http://legacysurvey.org/) are a combination of three public projects (the Dark Energy Camera Legacy Survey, the Beijing–Arizona Sky Survey, and the Mayall z-band Legacy Survey) that will jointly image ≈14,000 deg2 of the extragalactic sky visible from the northern hemisphere in three optical bands (g, r, and z) using telescopes at the Kitt Peak National Observatory and the Cerro Tololo Inter-American Observatory. The combined survey footprint is split into two contiguous areas by the Galactic plane. The optical imaging is conducted using a unique strategy of dynamically adjusting the exposure times and pointing selection during observing that results in a survey of nearly uniform depth. In addition to calibrated images, the project is delivering a catalog, constructed by using a probabilistic inference-based approach to estimate source shapes and brightnesses. The catalog includes photometry from the grz optical bands and from four mid-infrared bands (at 3.4, 4.6, 12, and 22 μm) observed by the Wide-field Infrared Survey Explorer satellite during its full operational lifetime. The project plans two public data releases each year. All the software used to generate the catalogs is also released with the data. This paper provides an overview of the Legacy Surveys project.
TL;DR: Advances in digital slide-based image diagnosis for cancer along with some challenges and opportunities for artificial intelligence in digital pathology are discussed.
Abstract: In modern clinical practice, digital pathology has a crucial role and is increasingly a technological requirement in the scientific laboratory environment. The advent of whole-slide imaging, availability of faster networks, and cheaper storage solutions has made it easier for pathologists to manage digital slide images and share them for clinical use. In parallel, unprecedented advances in machine learning have enabled the synergy of artificial intelligence and digital pathology, which offers image-based diagnosis possibilities that were once limited only to radiology and cardiology. Integration of digital slides into the pathology workflow, advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond a microscopic slide and enable true utilisation and integration of knowledge that is beyond human limits and boundaries, and we believe there is clear potential for artificial intelligence breakthroughs in the pathology setting. In this Review, we discuss advancements in digital slide-based image diagnosis for cancer along with some challenges and opportunities for artificial intelligence in digital pathology.
TL;DR: Evidence is provided to support recommendations for successful resistance training in older adults related to 4 parts: program design variables, physiological adaptations, functional benefits, and considerations for frailty, sarcopenia, and other chronic conditions.
Abstract: Fragala, MS, Cadore, EL, Dorgo, S, Izquierdo, M, Kraemer, WJ, Peterson, MD, and Ryan, ED. Resistance training for older adults: position statement from the national strength and conditioning association. J Strength Cond Res 33(8): 2019-2052, 2019-Aging, even in the absence of chronic disease, is associated with a variety of biological changes that can contribute to decreases in skeletal muscle mass, strength, and function. Such losses decrease physiologic resilience and increase vulnerability to catastrophic events. As such, strategies for both prevention and treatment are necessary for the health and well-being of older adults. The purpose of this Position Statement is to provide an overview of the current and relevant literature and provide evidence-based recommendations for resistance training for older adults. As presented in this Position Statement, current research has demonstrated that countering muscle disuse through resistance training is a powerful intervention to combat the loss of muscle strength and muscle mass, physiological vulnerability, and their debilitating consequences on physical functioning, mobility, independence, chronic disease management, psychological well-being, quality of life, and healthy life expectancy. This Position Statement provides evidence to support recommendations for successful resistance training in older adults related to 4 parts: (a) program design variables, (b) physiological adaptations, (c) functional benefits, and (d) considerations for frailty, sarcopenia, and other chronic conditions. The goal of this Position Statement is to a) help foster a more unified and holistic approach to resistance training for older adults, b) promote the health and functional benefits of resistance training for older adults, and c) prevent or minimize fears and other barriers to implementation of resistance training programs for older adults.
TL;DR: The development of titanium–copper alloys that have a high constitutional supercooling capacity as a result of partitioning of the alloying element during solidification, which can override the negative effect of a high thermal gradient in the laser-melted region during additive manufacturing.
Abstract: Additive manufacturing, often known as three-dimensional (3D) printing, is a process in which a part is built layer-by-layer and is a promising approach for creating components close to their final (net) shape. This process is challenging the dominance of conventional manufacturing processes for products with high complexity and low material waste1. Titanium alloys made by additive manufacturing have been used in applications in various industries. However, the intrinsic high cooling rates and high thermal gradient of the fusion-based metal additive manufacturing process often leads to a very fine microstructure and a tendency towards almost exclusively columnar grains, particularly in titanium-based alloys1. (Columnar grains in additively manufactured titanium components can result in anisotropic mechanical properties and are therefore undesirable2.) Attempts to optimize the processing parameters of additive manufacturing have shown that it is difficult to alter the conditions to promote equiaxed growth of titanium grains3. In contrast with other common engineering alloys such as aluminium, there is no commercial grain refiner for titanium that is able to effectively refine the microstructure. To address this challenge, here we report on the development of titanium-copper alloys that have a high constitutional supercooling capacity as a result of partitioning of the alloying element during solidification, which can override the negative effect of a high thermal gradient in the laser-melted region during additive manufacturing. Without any special process control or additional treatment, our as-printed titanium-copper alloy specimens have a fully equiaxed fine-grained microstructure. They also display promising mechanical properties, such as high yield strength and uniform elongation, compared to conventional alloys under similar processing conditions, owing to the formation of an ultrafine eutectoid microstructure that appears as a result of exploiting the high cooling rates and multiple thermal cycles of the manufacturing process. We anticipate that this approach will be applicable to other eutectoid-forming alloy systems, and that it will have applications in the aerospace and biomedical industries.
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Pennsylvania3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, Yale University13, Washington University in St. Louis14, University of California, San Francisco15, Roswell Park Cancer Institute16, Vanderbilt University17, University of Nebraska Medical Center18, Harvard University19, University of Wisconsin-Madison20, University of Michigan21, Stanford University22, Ohio State University23, University of California, San Diego24, City of Hope National Medical Center25, Memorial Sloan Kettering Cancer Center26, Mayo Clinic27, University of Tennessee Health Science Center28, National Comprehensive Cancer Network29
TL;DR: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) as discussed by the authors address all aspects of management for NSCLC, focusing on recent updates in immunotherapy.
Abstract: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."
TL;DR: It is shown that TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infection, and provide a link between the suppression of effector function intrinsic to CD8 T cells and protection against immunopathology.
Abstract: Cytotoxic T cells are essential mediators of protective immunity to viral infection and malignant tumours and are a key target of immunotherapy approaches. However, prolonged exposure to cognate antigens often attenuates the effector capacity of T cells and limits their therapeutic potential1-4. This process, known as T cell exhaustion or dysfunction1, is manifested by epigenetically enforced changes in gene regulation that reduce the expression of cytokines and effector molecules and upregulate the expression of inhibitory receptors such as programmed cell-death 1 (PD-1)5-8. The underlying molecular mechanisms that induce and stabilize the phenotypic and functional features of exhausted T cells remain poorly understood9-12. Here we report that the development and maintenance of populations of exhausted T cells in mice requires the thymocyte selection-associated high mobility group box (TOX) protein13-15. TOX is induced by high antigen stimulation of the T cell receptor and correlates with the presence of an exhausted phenotype during chronic infections with lymphocytic choriomeningitis virus in mice and hepatitis C virus in humans. Removal of its DNA-binding domain reduces the expression of PD-1 at the mRNA and protein level, augments the production of cytokines and results in a more polyfunctional T cell phenotype. T cells with this deletion initially mediate increased effector function and cause more severe immunopathology, but ultimately undergo a massive decline in their quantity, notably among the subset of TCF-1+ self-renewing T cells. Altogether, we show that TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infection, and provide a link between the suppression of effector function intrinsic to CD8 T cells and protection against immunopathology.
TL;DR: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide and can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Abstract: Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Memorial Sloan Kettering Cancer Center1, University of Texas MD Anderson Cancer Center2, Harvard University3, Seattle Cancer Care Alliance4, University of Michigan5, University of Pennsylvania6, Northwestern University7, Huntsman Cancer Institute8, Washington University in St. Louis9, Mayo Clinic10, University of California, San Diego11, Stanford University12, University of Wisconsin-Madison13, University of Nebraska Medical Center14, University of Colorado Boulder15, Ohio State University16, Case Western Reserve University17, University of Tennessee Health Science Center18, National Comprehensive Cancer Network19
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
Abstract: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.
TL;DR: The LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss than the other subtypes, and was classified as a mesenchymal-like subtype.