Showing papers by "Ohio State University published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: Evaluating the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1).
Abstract: The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair–deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.
4,569 citations
University of Ulm1, Fred Hutchinson Cancer Research Center2, King's College London3, University of Rome Tor Vergata4, University of Münster5, Brigham and Women's Hospital6, University of Chicago7, Memorial Sloan Kettering Cancer Center8, Leipzig University9, VU University Amsterdam10, University of Valencia11, National Taiwan University12, Alfred Hospital13, Monash University14, Erasmus University Medical Center15, Ohio State University16
TL;DR: An international panel to provide updated evidence- and expert opinion-based recommendations for diagnosis and management of acute myeloid leukemia in adults includes a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
4,066 citations
Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
Carnegie Mellon University1, Leibniz Institute for Astrophysics Potsdam2, Lawrence Berkeley National Laboratory3, New Mexico State University4, Sternberg Astronomical Institute5, Ohio State University6, University of Utah7, Yale University8, Autonomous University of Madrid9, University of Barcelona10, Harvard University11, Aix-Marseille University12, University of Paris13, Pierre-and-Marie-Curie University14, Max Planck Society15, University of California, Berkeley16, University of California, Irvine17, University of Portsmouth18, University of Cambridge19, Spanish National Research Council20, University of La Laguna21, Institut d'Astrophysique de Paris22, Princeton University23, University of Edinburgh24, Sejong University25, Kansas State University26, Pennsylvania State University27, National Scientific and Technical Research Council28, National University of La Plata29, Ohio University30, Brookhaven National Laboratory31, New York University32, University of St Andrews33, National Autonomous University of Mexico34, University of Wisconsin-Madison35, Open University36, Chinese Academy of Sciences37, University of Pittsburgh38, Case Western Reserve University39
TL;DR: In this article, the authors present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III.
Abstract: We present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. Our combined galaxy sample comprises 1.2 million massive galaxies over an effective area of 9329 deg^2 and volume of 18.7 Gpc^3, divided into three partially overlapping redshift slices centred at effective redshifts 0.38, 0.51 and 0.61. We measure the angular diameter distance and Hubble parameter H from the baryon acoustic oscillation (BAO) method, in combination with a cosmic microwave background prior on the sound horizon scale, after applying reconstruction to reduce non-linear effects on the BAO feature. Using the anisotropic clustering of the pre-reconstruction density field, we measure the product D_MH from the Alcock–Paczynski (AP) effect and the growth of structure, quantified by fσ_8(z), from redshift-space distortions (RSD). We combine individual measurements presented in seven companion papers into a set of consensus values and likelihoods, obtaining constraints that are tighter and more robust than those from any one method; in particular, the AP measurement from sub-BAO scales sharpens constraints from post-reconstruction BAOs by breaking degeneracy between D_M and H. Combined with Planck 2016 cosmic microwave background measurements, our distance scale measurements simultaneously imply curvature Ω_K = 0.0003 ± 0.0026 and a dark energy equation-of-state parameter w = −1.01 ± 0.06, in strong affirmation of the spatially flat cold dark matter (CDM) model with a cosmological constant (ΛCDM). Our RSD measurements of fσ_8, at 6 per cent precision, are similarly consistent with this model. When combined with supernova Ia data, we find H_0 = 67.3 ± 1.0 km s^−1 Mpc^−1 even for our most general dark energy model, in tension with some direct measurements. Adding extra relativistic species as a degree of freedom loosens the constraint only slightly, to H_0 = 67.8 ± 1.2 km s^−1 Mpc^−1. Assuming flat ΛCDM, we find Ω_m = 0.310 ± 0.005 and H_0 = 67.6 ± 0.5 km s^−1 Mpc^−1, and we find a 95 per cent upper limit of 0.16 eV c^−2 on the neutrino mass sum.
2,413 citations
Ohio State University1, Vanderbilt University2, Heidelberg University3, Iuliu Hațieganu University of Medicine and Pharmacy4, Duke University5, University of Lausanne6, Lehigh University7, McMaster University8, Fox Chase Cancer Center9, University of Texas at Austin10, Nemocnice Na Bulovce11, Bristol-Myers Squibb12
TL;DR: Nivolumab was not associated with significantly longer progression‐free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD‐L1 expression level of 5% or more.
Abstract: BackgroundNivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non–small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)–positive NSCLC. MethodsWe randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. ResultsAmong the 423 patients with a PD-L1 expression level of 5% or more, the media...
1,840 citations
The Nature Conservancy1, James Madison University2, Woods Hole Research Center3, Ohio State University4, Institute of Ecosystem Studies5, Resources For The Future6, University of Aberdeen7, Cornell University8, Colorado State University9, World Resources Institute10, Swedish University of Agricultural Sciences11, University of Minnesota12, University of Maryland, College Park13, University of Florida14, Wetlands International15, University of Vermont16
TL;DR: It is shown that NCS can provide over one-third of the cost-effective climate mitigation needed between now and 2030 to stabilize warming to below 2 °C.
Abstract: Better stewardship of land is needed to achieve the Paris Climate Agreement goal of holding warming to below 2 °C; however, confusion persists about the specific set of land stewardship options available and their mitigation potential. To address this, we identify and quantify "natural climate solutions" (NCS): 20 conservation, restoration, and improved land management actions that increase carbon storage and/or avoid greenhouse gas emissions across global forests, wetlands, grasslands, and agricultural lands. We find that the maximum potential of NCS-when constrained by food security, fiber security, and biodiversity conservation-is 23.8 petagrams of CO2 equivalent (PgCO2e) y-1 (95% CI 20.3-37.4). This is ≥30% higher than prior estimates, which did not include the full range of options and safeguards considered here. About half of this maximum (11.3 PgCO2e y-1) represents cost-effective climate mitigation, assuming the social cost of CO2 pollution is ≥100 USD MgCO2e-1 by 2030. Natural climate solutions can provide 37% of cost-effective CO2 mitigation needed through 2030 for a >66% chance of holding warming to below 2 °C. One-third of this cost-effective NCS mitigation can be delivered at or below 10 USD MgCO2-1 Most NCS actions-if effectively implemented-also offer water filtration, flood buffering, soil health, biodiversity habitat, and enhanced climate resilience. Work remains to better constrain uncertainty of NCS mitigation estimates. Nevertheless, existing knowledge reported here provides a robust basis for immediate global action to improve ecosystem stewardship as a major solution to climate change.
1,508 citations
Harvard University1, Mayo Clinic2, Duke University3, Ohio State University4, Hannover Medical School5, Monash University6, Autonomous University of Barcelona7, Radboud University Nijmegen8, Fred Hutchinson Cancer Research Center9, Stanford University10, Memorial Sloan Kettering Cancer Center11, University of Chicago12, University Health Network13, Leipzig University14, University of Ulm15, Goethe University Frankfurt16, Dresden University of Technology17, University of Rome Tor Vergata18
TL;DR: The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event‐free survival among patients with AML and a FLT3 mutation.
Abstract: BackgroundPatients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin — an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation — to standard chemotherapy would prolong overall survival in this population. MethodsWe screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of muta...
1,474 citations
TL;DR: In this article, the authors profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases.
1,425 citations
TL;DR: The goal of this paper is to nudge clinical researchers away from historically significant but increasingly old school approaches toward modifications, revisions, and extensions that characterize more modern thinking about the analysis of the mechanisms and contingencies of effects.
TL;DR: In this paper, the authors studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016.
Abstract: BackgroundIn 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. MethodsWe studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. ResultsAmong 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour...
Michael R. Blanton1, Matthew A. Bershady2, Bela Abolfathi3, Franco D. Albareti4 +412 more•Institutions (91)
TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
University of Virginia1, Liverpool John Moores University2, Texas Christian University3, University of La Laguna4, Spanish National Research Council5, Johns Hopkins University6, New Mexico State University7, Sternberg Astronomical Institute8, University of Arizona9, Ohio State University10, Pennsylvania State University11, University of Wisconsin-Madison12, Eötvös Loránd University13, University of Toronto14, University of Michigan15, University of Texas at Austin16, Leibniz Institute for Astrophysics Potsdam17, Yale University18, University of Colorado Boulder19, New York University20, Princeton University21, University of Utah22, Goddard Space Flight Center23, University of Birmingham24, Aarhus University25, Harvard University26, Computer Sciences Corporation27, Space Telescope Science Institute28, Paris Diderot University29, INAF30, Max Planck Society31, Space Science Institute32, Pierre-and-Marie-Curie University33, University of Franche-Comté34, Federal University of Rio de Janeiro35, University of Nice Sophia Antipolis36
TL;DR: In this article, the Hungarian National Research, Development and Innovation Office (K-119517) and Hungarian National Science Foundation (KNFI) have proposed a method to detect the presence of asteroids in Earth's magnetic field.
Abstract: National Science Foundation [AST-1109178, AST-1616636]; Gemini Observatory; Spanish Ministry of Economy and Competitiveness [AYA-2011-27754]; NASA [NNX12AE17G]; Hungarian Academy of Sciences; Hungarian NKFI of the Hungarian National Research, Development and Innovation Office [K-119517]; Alfred P. Sloan Foundation; National Science Foundation; U.S. Department of Energy Office of Science
TL;DR: There remains growing interest in magnesium (Mg) and its alloys, as they are the lightest structural metallic materials Mg alloys have the potential to enable design of lighter engineered systems, including positive implications for reduced energy consumption as mentioned in this paper.
University of Texas MD Anderson Cancer Center1, Princess Margaret Cancer Centre2, Memorial Sloan Kettering Cancer Center3, Hebron University4, European Institute of Oncology5, Ottawa Hospital Research Institute6, University of Manchester7, Catholic University of the Sacred Heart8, French Institute of Health and Medical Research9, Auckland City Hospital10, Royal Brisbane and Women's Hospital11, Ohio State University12, Johns Hopkins University13, University of Washington14, University of California, Los Angeles15, University of Glasgow16, Royal Melbourne Hospital17, Foundation Medicine18, University College London19, Ghent University Hospital20
TL;DR: This trial assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity.
TL;DR: In this work, a 13-layer deep convolutional neural network (CNN) algorithm is implemented to detect normal, preictal, and seizure classes and achieved an accuracy, specificity, and sensitivity of 88.67%, 90.00% and 95.00%, respectively.
TL;DR: This paper will provide psychophysiological researchers with recommendations and practical advice concerning experimental designs, data analysis, and data reporting to ensure that researchers starting a project with HRV and cardiac vagal tone are well informed regarding methodological considerations in order for their findings to contribute to knowledge advancement in their field.
Abstract: Psychophysiological research integrating heart rate variability (HRV) has increased during the last two decades, particularly given the fact that HRV is able to index cardiac vagal tone. Vagal tone, which represents the activity of the parasympathetic system, is acknowledged to be linked with many phenomena relevant for psychophysiological research, including self-regulation at the cognitive, emotional, social, and health levels. The ease of HRV collection and measurement coupled with the fact it is relatively affordable, non-invasive and pain free makes it widely accessible to many researchers. This ease of access should not obscure the difficulty of interpretation of HRV findings that can be easily misconstrued, however this can be controlled to some extent through correct methodological processes. Standards of measurement were developed two decades ago by a Task Force within HRV research, and recent reviews updated several aspects of the Task Force paper. However, many methodological aspects related to HRV in psychophysiological research have to be considered if one aims to be able to draw sound conclusions, which makes it difficult to interpret findings and to compare results across laboratories. Those methodological issues have mainly been discussed in separate outlets, making difficult to get a grasp on them, and thus this paper aims to address this issue. It will help to provide psychophysiological researchers with recommendations and practical advice concerning experimental designs, data analysis, and data reporting. This will ensure that researchers starting a project with HRV and cardiac vagal tone are well informed regarding methodological considerations in order for their findings to contribute to knowledge advancement in their field.
TL;DR: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.
Abstract: Background Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. Methods In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. Results Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analys...
TL;DR: This Review focuses on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells.
Abstract: Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials and indicates the need for multi-targeted or combinatorial therapies. In this Review, we focus on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment.
TL;DR: Novel concepts and paradigms are described here that have emerged, targeting superior TE materials and higher TE performance, including band convergence, "phonon-glass electron-crystal", multiscale phonon scattering, resonant states, anharmonicity, etc.
Abstract: The past two decades have witnessed the rapid growth of thermoelectric (TE) research. Novel concepts and paradigms are described here that have emerged, targeting superior TE materials and higher TE performance. These superior aspects include band convergence, "phonon-glass electron-crystal", multiscale phonon scattering, resonant states, anharmonicity, etc. Based on these concepts, some new TE materials with distinct features have been identified, including solids with high band degeneracy, with cages in which atoms rattle, with nanostructures at various length scales, etc. In addition, the performance of classical materials has been improved remarkably. However, the figure of merit zT of most TE materials is still lower than 2.0, generally around 1.0, due to interrelated TE properties. In order to realize an "overall zT > 2.0," it is imperative that the interrelated properties are decoupled more thoroughly, or new degrees of freedom are added to the overall optimization problem. The electrical and thermal transport must be synergistically optimized. Here, a detailed discussion about the commonly adopted strategies to optimize individual TE properties is presented. Then, four main compromises between the TE properties are elaborated from the point of view of the underlying mechanisms and decoupling strategies. Finally, some representative systems of synergistic optimization are also presented, which can serve as references for other TE materials. In conclusion, some of the newest ideas for the future are discussed.
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Colorado Boulder3, University of Utah4, Fox Chase Cancer Center5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of South Florida9, University of Alabama at Birmingham10, Washington University in St. Louis11, University of California, San Francisco12, Roswell Park Cancer Institute13, Vanderbilt University14, University of Texas MD Anderson Cancer Center15, Harvard University16, University of Wisconsin-Madison17, Yale Cancer Center18, University of Michigan19, Stanford University20, Ohio State University21, City of Hope National Medical Center22, Memorial Sloan Kettering Cancer Center23, Mayo Clinic24, Case Western Reserve University25, University Of Tennessee System26
TL;DR: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastasis disease.
Abstract: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.
University of California, Los Angeles1, University of Utah2, University of South Florida3, University of Helsinki4, Primary Children's Hospital5, University of Groningen6, Norfolk and Norwich University Hospital7, Lund University8, Netherlands Cancer Institute9, University of Michigan10, Wake Forest University11, Ohio State University12, Peter MacCallum Cancer Centre13, University of Zurich14, University of Padua15, Pennsylvania State University16, Saint Louis University17, Tom Baker Cancer Centre18, University of Washington19, University of Lausanne20, Guy's and St Thomas' NHS Foundation Trust21, University of Kiel22, Thomas Jefferson University23, Sunnybrook Research Institute24, Vanderbilt University25, University of Queensland26, Fox Chase Cancer Center27, Greenville Health System28, Stony Brook University29, University Health Network30, Memorial Sloan Kettering Cancer Center31, Roswell Park Cancer Institute32, Northwestern University33, University of Wisconsin-Madison34, Rush University Medical Center35, Tel Aviv Sourasky Medical Center36, Dartmouth College37, Johns Hopkins University38, University of Louisville39, University of Barcelona40, University of Sydney41
TL;DR: Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases.
Abstract: BackgroundSentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. MethodsIn an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. ResultsImmediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in t...
University of Washington1, Princess Margaret Cancer Centre2, Royal Melbourne Hospital3, Foundation Medicine4, University of California, Los Angeles5, University of Texas MD Anderson Cancer Center6, BC Cancer Agency7, Ohio State University8, University College London9, Memorial Sloan Kettering Cancer Center10, University of Cambridge11, University of Arizona12, Hebron University13, Mayo Clinic14, Institut Gustave Roussy15, University of Glasgow16
TL;DR: The ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor, was assessed in ARIEL2, an international, multicentre, two-part, phase 2, open-label study.
Abstract: Summary Background Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. Methods ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. Findings 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8–10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0–14·7) in the BRCA mutant subgroup, 5·7 months (5·3–7·6) in the LOH high subgroup, and 5·2 months (3·6–5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16–0·44, p Interpretation In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours. Funding Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer—Ovarian Cancer Research Fund Alliance—National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award.
TL;DR: This exploratory, extended-duration treatment protocol appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD.
Abstract: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number
NCT02504554
TL;DR: In this paper, the authors study how to optimally manage the freshness of information updates sent from a source node to a destination via a channel and develop efficient algorithms to find the optimal update policy among all causal policies and establish sufficient and necessary conditions for the optimality of the zero-wait policy.
Abstract: In this paper, we study how to optimally manage the freshness of information updates sent from a source node to a destination via a channel. A proper metric for data freshness at the destination is the age-of-information , or simply age , which is defined as how old the freshest received update is, since the moment that this update was generated at the source node (e.g., a sensor). A reasonable update policy is the zero-wait policy, i.e., the source node submits a fresh update once the previous update is delivered, which achieves the maximum throughput and the minimum delay. Surprisingly, this zero-wait policy does not always minimize the age. This counter-intuitive phenomenon motivates us to study how to optimally control information updates to keep the data fresh and to understand when the zero-wait policy is optimal. We introduce a general age penalty function to characterize the level of dissatisfaction on data staleness and formulate the average age penalty minimization problem as a constrained semi-Markov decision problem with an uncountable state space. We develop efficient algorithms to find the optimal update policy among all causal policies and establish sufficient and necessary conditions for the optimality of the zero-wait policy. Our investigation shows that the zero-wait policy is far from the optimum if: 1) the age penalty function grows quickly with respect to the age; 2) the packet transmission times over the channel are positively correlated over time; or 3) the packet transmission times are highly random (e.g., following a heavy-tail distribution).
TL;DR: In this paper, the authors describe a web interface that provides an up-to-date aperture photometry light curve for any user-selected sky coordinate, which can only be used for small samples of objects.
Abstract: The All-Sky Automated Survey for Supernovae (ASAS-SN) is working towards imaging the entire visible sky every night to a depth of V~17 mag. The present data covers the sky and spans ~2-5~years with ~100-400 epochs of observation. The data should contain some ~1 million variable sources, and the ultimate goal is to have a database of these observations publicly accessible. We describe here a first step, a simple but unprecedented web interface https://asas-sn.osu.edu/ that provides an up to date aperture photometry light curve for any user-selected sky coordinate. Because the light curves are produced in real time, this web tool is relatively slow and can only be used for small samples of objects. However, it also imposes no selection bias on the part of the ASAS-SN team, allowing the user to obtain a light curve for any point on the celestial sphere. We present the tool, describe its capabilities, limitations, and known issues, and provide a few illustrative examples.
TL;DR: In this article, the Gordon and Betty Moore Foundation (GBMF5076) and the Heising-Simons Foundation (HSPF) have contributed to the creation of the DES-Brazil Consortium.
Abstract: NSF [AST-1411763, AST-1714498, DGE 1144152, PHY-1707954, AST-1518052]; NASA [NNX15AE50G, NNX16AC22G]; National Science Foundation; Kavli Foundation; Danish National Research Foundation; Niels Bohr International Academy; DARK Cosmology Centre; Gordon & Betty Moore Foundation; Heising-Simons Foundation; UCSC; Alfred P. Sloan Foundation; David and Lucile Packard Foundation; European Research Council [ERC-StG-335936]; Gordon and Betty Moore Foundation [GBMF5076]; DOE (USA); NSF (USA); MISE (Spain); STFC (UK); HEFCE (UK); NCSA (UIUC); KICP (U. Chicago); CCAPP (Ohio State); MIFPA (Texas AM); MINECO (Spain); DFG (Germany); CNPQ (Brazil); FAPERJ (Brazil); FINEP (Brazil); Argonne Lab; UC Santa Cruz; University of Cambridge; CIEMAT-Madrid; University of Chicago; University College London; DES-Brazil Consortium; University of Edinburgh; ETH Zurich; Fermilab; University of Illinois; ICE (IEEC-CSIC); IFAE Barcelona; Lawrence Berkeley Lab; LMU Munchen; Excellence Cluster Universe; University of Michigan; NOAO; University of Nottingham; Ohio State University; University of Pennsylvania; University of Portsmouth; SLAC National Lab; Stanford University; University of Sussex; Texas AM University; Gemini Observatory [GS-2017B-Q-8, GS-2017B-DD-4]
TL;DR: This paper answers a few frequently-asked questions about the difference between PROCESS and structural equation modeling and shows by way of example that, for observed variable models, the choice of which to use is inconsequential, as the results are largely identical.
Abstract: Marketing, consumer, and organizational behavior researchers interested in studying the mechanisms by which effects operate and the conditions that enhance or inhibit such effects often rely on sta...
03 Oct 2017
TL;DR: Evidence of as-yet-unappreciated MSI in several types of cancer support an expanded role for clinical MSI testing across multiple cancer types as patients with MSI-positive tumors are predicted to benefit from novel immunotherapies in clinical trials.
Abstract: PurposeMicrosatellite instability (MSI) is a pattern of hypermutation that occurs at genomic microsatellites and is caused by defects in the mismatch repair system. Mismatch repair deficiency that leads to MSI has been well described in several types of human cancer, most frequently in colorectal, endometrial, and gastric adenocarcinomas. MSI is known to be both predictive and prognostic, especially in colorectal cancer; however, current clinical guidelines only recommend MSI testing for colorectal and endometrial cancers. Therefore, less is known about the prevalence and extent of MSI among other types of cancer.MethodsUsing our recently published MSI-calling software, MANTIS, we analyzed whole-exome data from 11,139 tumor-normal pairs from The Cancer Genome Atlas and Therapeutically Applicable Research to Generate Effective Treatments projects and external data sources across 39 cancer types. Within a subset of these cancer types, we assessed mutation burden, mutational signatures, and somatic variants ...