Showing papers by "University of Utah published in 2017"
TL;DR: The scope and purpose of this work is to synthesize the available evidence and to translate it into recommendations, so that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient.
Abstract: The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.
2,703 citations
Carnegie Mellon University1, Leibniz Institute for Astrophysics Potsdam2, Lawrence Berkeley National Laboratory3, Sternberg Astronomical Institute4, New Mexico State University5, Ohio State University6, University of Utah7, Yale University8, Autonomous University of Madrid9, University of Barcelona10, Harvard University11, Aix-Marseille University12, Pierre-and-Marie-Curie University13, University of Paris14, Max Planck Society15, University of California, Berkeley16, University of California, Irvine17, University of Portsmouth18, University of Cambridge19, University of La Laguna20, Spanish National Research Council21, 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, Open University35, University of Wisconsin-Madison36, 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
Imperial College London1, Anglia Ruskin University2, University of New South Wales3, Brien Holden Vision Institute4, International Agency for the Prevention of Blindness5, Moorfields Eye Hospital6, York Hospital7, Heidelberg University8, L V Prasad Eye Institute9, Massachusetts Eye and Ear Infirmary10, Nova Southeastern University11, University of KwaZulu-Natal12, National Health and Medical Research Council13, World Health Organization14, National University of Singapore15, University of Melbourne16, Selçuk University17, University of Miami18, University of Adelaide19, Queen's University Belfast20, Harvard University21, The George Institute for Global Health22, University of Washington23, University of Michigan24, Universiti Tunku Abdul Rahman25, University of Alabama at Birmingham26, National Institutes of Health27, Johns Hopkins University28, University of São Paulo29, Henry Ford Health System30, University College London31, Sankara Nethralaya32, University of Nairobi33, University of Georgia34, University of Utah35, Federal University of São Paulo36, Yale University37, Alberta Children's Hospital38, University of Illinois at Chicago39, Medical College of Wisconsin40, Novartis41, University of Udine42, University of Illinois at Urbana–Champaign43, Royal Children's Hospital44, University of Missouri45, Centers for Disease Control and Prevention46, University of Milan47, Icahn School of Medicine at Mount Sinai48, Mayo Clinic49, Pan American Health Organization50, University of Indonesia51, University of Pennsylvania52, University of Crete53, University of Southern California54, University of Florence55, Capital Medical University56, Leipzig University57
TL;DR: A series of regression models were fitted to estimate the proportion of moderate or severe vision impairment and blindness by cause, age, region, and year, and found that world regions varied markedly in the causes of blindness and vision impairment in this age group.
1,909 citations
TL;DR: UpSetR is an open source R package that employs a scalable matrix‐based visualization to show intersections of sets, their size, and other properties, and is released under the MIT License.
Abstract: Motivation Venn and Euler diagrams are a popular yet inadequate solution for quantitative visualization of set intersections. A scalable alternative to Venn and Euler diagrams for visualizing intersecting sets and their properties is needed. Results We developed UpSetR, an open source R package that employs a scalable matrix-based visualization to show intersections of sets, their size, and other properties. Availability and implementation UpSetR is available at https://github.com/hms-dbmi/UpSetR/ and released under the MIT License. A Shiny app is available at https://gehlenborglab.shinyapps.io/upsetr/ . Contact nils@hms.harvard.edu. Supplementary information Supplementary data are available at Bioinformatics online.
1,760 citations
University of Cambridge1, Wellcome Trust Sanger Institute2, University of Melbourne3, Netherlands Cancer Institute4, University of Amsterdam5, University of Warwick6, Cancer Council Victoria7, University of Utah8, Columbia University9, Central Manchester University Hospitals NHS Foundation Trust10, Chapel Allerton Hospital11, Guy's and St Thomas' NHS Foundation Trust12, National Institute for Health Research13, University of Glasgow14, St George's, University of London15, Curie Institute16, Paris Descartes University17, Erasmus University Rotterdam18, Radboud University Nijmegen19, VU University Medical Center20, Cancer Prevention Institute of California21, Lunenfeld-Tanenbaum Research Institute22, University of Toronto23, Fox Chase Cancer Center24, Huntsman Cancer Institute25, Leipzig University26, German Cancer Research Center27, University of Cologne28, Hospital Clínico San Carlos29, Pomeranian Medical University30, Laval University31, University of New South Wales32, St. Vincent's Health System33, Peter MacCallum Cancer Centre34, QIMR Berghofer Medical Research Institute35, Medical University of Vienna36, Copenhagen University Hospital37, Karolinska Institutet38, Lund University39
TL;DR: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location, a large cohort study recruited in 1997-2011 provides estimates of cancer risk based on BRCA1 and BRCa2 mutation carrier status.
Abstract: Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. Exposures: BRCA1/2 mutations, family cancer history, and mutation location. Main Outcomes and Measures: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Results: Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and Relevance: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
1,733 citations
Anglia Ruskin University1, University of Oxford2, Heidelberg University3, L V Prasad Eye Institute4, Massachusetts Eye and Ear Infirmary5, Nova Southeastern University6, Brien Holden Vision Institute7, University of KwaZulu-Natal8, Flinders University9, University of New South Wales10, Royal Liverpool University Hospital11, World Health Organization12, National University of Singapore13, University of Melbourne14, Selçuk University15, University of Burgundy16, University of Miami17, University of Adelaide18, Queen's University Belfast19, Harvard University20, The George Institute for Global Health21, University of Washington22, University of Michigan23, Universiti Tunku Abdul Rahman24, University of Alabama25, National Institutes of Health26, Johns Hopkins University27, University of São Paulo28, Henry Ford Health System29, University College London30, University of Nairobi31, University of Georgia32, University of Utah33, Federal University of São Paulo34, Yale University35, Alberta Children's Hospital36, University of Pennsylvania37, Medical College of Wisconsin38, Novartis39, University of Udine40, University of Illinois at Urbana–Champaign41, Royal Children's Hospital42, University of Missouri43, University of Milan44, Centers for Disease Control and Prevention45, Singapore National Eye Center46, Icahn School of Medicine at Mount Sinai47, Mayo Clinic48, Pan American Health Organization49, University of Indonesia50, University of Crete51, Erasmus University Rotterdam52, University of Southern California53, University of Florence54, Stellenbosch University55, Capital Medical University56, Leipzig University57, Moorfields Eye Hospital58
TL;DR: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected, highlighting the need to scale up vision impairment alleviation efforts at all levels.
1,473 citations
TL;DR: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease and confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms.
Abstract: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.
1,322 citations
TL;DR: A new study reveals that additional pheromone cues released only by younger females may prompt males to avoid them in favor of older but more fecund females.
1,208 citations
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.
1,200 citations
University of Virginia1, Liverpool John Moores University2, Texas Christian University3, Spanish National Research Council4, University of La Laguna5, 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, Aarhus University24, University of Birmingham25, Harvard University26, Space Telescope Science Institute27, Computer Sciences Corporation28, 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
1,193 citations
Kyriaki Michailidou1, Kyriaki Michailidou2, Sara Lindström3, Sara Lindström4 +393 more•Institutions (127)
TL;DR: A genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry finds that heritability of Breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome- wide average.
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
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.
TL;DR: Recent findings supporting the long-standing hypothesis that the waves of TE invasions endured by organisms for eons have catalysed the evolution of gene-regulatory networks are reviewed.
Abstract: Transposable elements (TEs) are widely known for their deleterious consequences of selfish propagation and mutagenesis. However, as described in this Review, TEs also provide hosts with rich, beneficial gene-regulatory machinery in the form of regulatory DNA elements and TE-derived gene products. The authors highlight the diverse regulatory contributions of TEs to organismal physiology and pathology, provide a framework for responsibly assigning functional roles to TEs and offer visions for the future.
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 Marburg1, University of Erlangen-Nuremberg2, Rovira i Virgili University3, Max Planck Society4, University of Göttingen5, University of California, Los Angeles6, International School for Advanced Studies7, University of Melbourne8, University of Trieste9, Ikerbasque10, University of Toronto11, Nanyang Technological University12, National Institutes of Health13, Stanford University14, Shanghai Jiao Tong University15, Tongji University16, University of Seville17, Karolinska Institutet18, Drexel University19, Sichuan University20, Rice University21, Northwestern University22, University of Basel23, Zhejiang University24, Heidelberg University25, University of Tokyo26, Harvard University27, University of Utah28, University of Michigan29, Swiss Federal Laboratories for Materials Science and Technology30, Seoul National University31, Saarland University32, Columbia University33, Chinese Academy of Sciences34, Kazan Federal University35, Emory University36, University of California, Irvine37, Autonomous University of Barcelona38, University of Massachusetts Amherst39, Pennsylvania State University40, Ghent University41, Imperial College London42, National Tsing Hua University43, South China University of Technology44, University of Ulm45, Hebrew University of Jerusalem46, Huazhong University of Science and Technology47, Peking University48
TL;DR: An overview of recent developments in nanomedicine is provided and the current challenges and upcoming opportunities for the field are highlighted and translation to the clinic is highlighted.
Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
30 Oct 2017
TL;DR: DeepLog, a deep neural network model utilizing Long Short-Term Memory (LSTM), is proposed, to model a system log as a natural language sequence, which allows DeepLog to automatically learn log patterns from normal execution, and detect anomalies when log patterns deviate from the model trained from log data under normal execution.
Abstract: Anomaly detection is a critical step towards building a secure and trustworthy system. The primary purpose of a system log is to record system states and significant events at various critical points to help debug system failures and perform root cause analysis. Such log data is universally available in nearly all computer systems. Log data is an important and valuable resource for understanding system status and performance issues; therefore, the various system logs are naturally excellent source of information for online monitoring and anomaly detection. We propose DeepLog, a deep neural network model utilizing Long Short-Term Memory (LSTM), to model a system log as a natural language sequence. This allows DeepLog to automatically learn log patterns from normal execution, and detect anomalies when log patterns deviate from the model trained from log data under normal execution. In addition, we demonstrate how to incrementally update the DeepLog model in an online fashion so that it can adapt to new log patterns over time. Furthermore, DeepLog constructs workflows from the underlying system log so that once an anomaly is detected, users can diagnose the detected anomaly and perform root cause analysis effectively. Extensive experimental evaluations over large log data have shown that DeepLog has outperformed other existing log-based anomaly detection methods based on traditional data mining methodologies.
University of Jena1, University of Chicago2, Fred Hutchinson Cancer Research Center3, University of South Australia4, University of Adelaide5, University of Bologna6, University of Utah7, University of Barcelona8, Novartis9, University of Texas MD Anderson Cancer Center10, Newcastle University11, Oregon Health & Science University12
TL;DR: Almost 11 years of follow-up showed that the efficacy of Imatinib persisted over time and that long‐term administration of imatinib was not associated with unacceptable cumulative or late toxic effects.
Abstract: BackgroundImatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy. MethodsIn this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events. ResultsThe median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall s...
TL;DR: Optimal searches in systematic reviews should search at least Embase, MEDLINE, Web of Science, and Google Scholar as a minimum requirement to guarantee adequate and efficient coverage.
Abstract: Within systematic reviews, when searching for relevant references, it is advisable to use multiple databases. However, searching databases is laborious and time-consuming, as syntax of search strategies are database specific. We aimed to determine the optimal combination of databases needed to conduct efficient searches in systematic reviews and whether the current practice in published reviews is appropriate. While previous studies determined the coverage of databases, we analyzed the actual retrieval from the original searches for systematic reviews. Since May 2013, the first author prospectively recorded results from systematic review searches that he performed at his institution. PubMed was used to identify systematic reviews published using our search strategy results. For each published systematic review, we extracted the references of the included studies. Using the prospectively recorded results and the studies included in the publications, we calculated recall, precision, and number needed to read for single databases and databases in combination. We assessed the frequency at which databases and combinations would achieve varying levels of recall (i.e., 95%). For a sample of 200 recently published systematic reviews, we calculated how many had used enough databases to ensure 95% recall. A total of 58 published systematic reviews were included, totaling 1746 relevant references identified by our database searches, while 84 included references had been retrieved by other search methods. Sixteen percent of the included references (291 articles) were only found in a single database; Embase produced the most unique references (n = 132). The combination of Embase, MEDLINE, Web of Science Core Collection, and Google Scholar performed best, achieving an overall recall of 98.3 and 100% recall in 72% of systematic reviews. We estimate that 60% of published systematic reviews do not retrieve 95% of all available relevant references as many fail to search important databases. Other specialized databases, such as CINAHL or PsycINFO, add unique references to some reviews where the topic of the review is related to the focus of the database. Optimal searches in systematic reviews should search at least Embase, MEDLINE, Web of Science, and Google Scholar as a minimum requirement to guarantee adequate and efficient coverage.
University of California, San Francisco1, Moffitt Cancer Center2, University of Michigan3, Mayo Clinic4, Roswell Park Cancer Institute5, University of Tennessee Health Science Center6, Northwestern University7, Washington University in St. Louis8, Vanderbilt University9, Yale Cancer Center10, Seattle Cancer Care Alliance11, City of Hope National Medical Center12, Duke University13, Ohio State University14, Fox Chase Cancer Center15, Harvard University16, Case Western Reserve University17, University of Texas MD Anderson Cancer Center18, Stanford University19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Memorial Sloan Kettering Cancer Center23, University of Alabama at Birmingham24, University of Utah25, University of Colorado Boulder26, Dana Corporation27
TL;DR: The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection, as well as on management of locally advanced unresectable and metastatic disease.
Abstract: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
TL;DR: The 'hourglass' model of remodeller function is proposed, in which each remodeller subfamily utilizes diverse specialized proteins and protein domains to assist in nucleosomes targeting or to differentially detect nucleosome epitopes.
Abstract: Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation. We propose the 'hourglass' model of remodeller function, in which each remodeller subfamily utilizes diverse specialized proteins and protein domains to assist in nucleosome targeting or to differentially detect nucleosome epitopes. These modules converge to regulate a common DNA translocation mechanism, to inform the conserved ATPase 'motor' on whether and how to apply DNA translocation, which together achieve the various outcomes of chromatin remodelling: nucleosome assembly, chromatin access and nucleosome editing.
Oklahoma State University–Stillwater1, Macquarie University2, University of Sydney3, University of Utah4, Max Planck Society5, University of Alberta6, University of California, Irvine7, University of New Mexico8, University of Nebraska–Lincoln9, United States Geological Survey10, University of Washington11, University of Arizona12, University of Sheffield13, University of Tasmania14, ETH Zurich15, University of California, Davis16, Los Alamos National Laboratory17, Nanchang Institute of Technology18, University of Wyoming19, Swedish University of Agricultural Sciences20, University of Coimbra21, Northern Arizona University22, United States Forest Service23, Swiss Federal Institute for Forest, Snow and Landscape Research24, University of São Paulo25, University of Oxford26, University of California, Santa Cruz27, Humboldt State University28, Fordham University29, Centre national de la recherche scientifique30, University of Edinburgh31, Hobart Corporation32, Spanish National Research Council33, University of Chile34, Idaho State University35, University of Basilicata36, Colorado State University37, United States Department of Agriculture38, University of Montana39, University of Delaware40, Duke University41, University of Western Ontario42, Sonora Institute of Technology43, Pacific Northwest National Laboratory44
TL;DR: It is shown that, across multiple tree species, loss of xylem conductivity above 60% is associated with mortality, while carbon starvation is not universal, indicating that evidence supporting carbon starvation was not universal.
Abstract: Widespread tree mortality associated with drought has been observed on all forested continents and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analysed across species and biomes using a standardized physiological framework. Here, we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought-induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function.
University of California, San Diego1, Beth Israel Deaconess Medical Center2, University of Cambridge3, National Institutes of Health4, Cleveland Clinic5, University of Pennsylvania6, Mayo Clinic7, University of Barcelona8, Research Triangle Park9, University of Utah10, GlaxoSmithKline11, Harvard University12
TL;DR: In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use.
Abstract: BackgroundEosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis MethodsIn this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48 Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52) The annualized rel
TL;DR: This study showed long‐term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux‐en‐Y gastric bypass.
Abstract: BackgroundFew long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States. MethodsA total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia. ResultsThe follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was −45.0 kg (95% confidence interval [CI], −47.2 to −42.9; mean percent change, −35.0) at 2 years, −36.3 kg (95% CI, −39.0 to −33.5; mean percent change, −28...
Fox Chase Cancer Center1, Ohio State University2, University of Tennessee Health Science Center3, University of Utah4, University of Alabama5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of Colorado Boulder9, Stanford University10, University of Texas MD Anderson Cancer Center11, University of California, San Diego12, University of Michigan13, Memorial Sloan Kettering Cancer Center14, Moffitt Cancer Center15, Harvard University16, University of Washington17, Case Western Reserve University18, Roswell Park Cancer Institute19, City of Hope National Medical Center20, Mayo Clinic21, Vanderbilt University22, National Comprehensive Cancer Network23
TL;DR: The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
Abstract: The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
04 Sep 2017
TL;DR: In this article, the authors focus on proximate explanations without regard for ultimate factors which may, when viewed in the context of ecological characteristics and various proximate factors, and provide a broader and more satisfying answer to questions about paternal behavior in humans.
Abstract: This chapter focuses on proximate explanations —usually in terms of psychological or sociological factors —without regard for ultimate factors which may, when viewed in the context of ecological characteristics and various proximate factors, and provides a broader and more satisfying answer to questions about paternal behavior in humans. It also focuses on the factors affecting degree of paternal involvement, beginning with factors accounting for sex differences between men and women and proceeding to factors accounting for individual differences among men. As in most of the great debates in psychology, popular and scientific discussions of sex differences in parental behavior frequently degenerate into debates between simplistic environmental determinism and simplistic biological determinism, neither of which proves very helpful in understanding the phenomenon. Procreation must surely rank as one of the major activities involved in the attainment of inclusive fitness; it constitutes one of the most basic elements of fatherhood.
Yale University1, Harvard University2, Columbia University3, University College London4, University of California, San Francisco5, University of Toronto6, University of Michigan7, University of Pennsylvania8, Great Ormond Street Hospital9, University of Rochester10, University of Pittsburgh11, University of Utah12, University of Southern California13, National Institutes of Health14, Icahn School of Medicine at Mount Sinai15, Rockefeller University16
TL;DR: Exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent–offspring trios, implicated rare inherited mutations in 1.8%, and DNMs in ∼440 genes were inferred to contribute to CHD.
Abstract: Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.
TL;DR: The catalytic footprint of the grain boundary is commensurate with its dislocation-induced strain field, providing a strategy for broader exploitation of grain-boundary effects in heterogeneous catalysis.
Abstract: Altering a material’s catalytic properties requires identifying structural features that give rise to active surfaces. Grain boundaries create strained regions in polycrystalline materials by stabilizing dislocations and may provide a way to create high-energy surfaces for catalysis that are kinetically trapped. Although grain-boundary density has previously been correlated with catalytic activity for some reactions, direct evidence that grain boundaries create surfaces with enhanced activity is lacking. We used a combination of bulk electrochemical measurements and scanning electrochemical cell microscopy with submicrometer resolution to show that grain-boundary surface terminations in gold electrodes are more active than grain surfaces for electrochemical carbon dioxide (CO 2 ) reduction to carbon monoxide (CO) but not for the competing hydrogen (H 2 ) evolution reaction. The catalytic footprint of the grain boundary is commensurate with its dislocation-induced strain field, providing a strategy for broader exploitation of grain-boundary effects in heterogeneous catalysis.
Franco D. Albareti1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto2 +397 more•Institutions (95)
TL;DR: Data Release 13 (DR13) as discussed by the authors provides the first 1390 spatially resolved integral field unit observations of nearby galaxies from the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS).
Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in 2014 July. It pursues three core programs: the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS). As well as its core program, eBOSS contains two major subprograms: the Time Domain Spectroscopic Survey (TDSS) and the SPectroscopic IDentification of ERosita Sources (SPIDERS). This paper describes the first data release from SDSS-IV, Data Release 13 (DR13). DR13 makes publicly available the first 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA. It includes new observations from eBOSS, completing the Sloan Extended QUasar, Emission-line galaxy, Luminous red galaxy Survey (SEQUELS), which also targeted variability-selected objects and X-ray-selected objects. DR13 includes new reductions of the SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification, and new reductions of the SDSS-III APOGEE-1 data, improving stellar parameters for dwarf stars and cooler stars. DR13 provides more robust and precise photometric calibrations. Value-added target catalogs relevant for eBOSS, TDSS, and SPIDERS and an updated red-clump catalog for APOGEE are also available. This paper describes the location and format of the data and provides references to important technical papers. The SDSS web site, http://www.sdss.org, provides links to the data, tutorials, examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ∼6 yr operations of SDSS-IV.
The Catholic University of America1, University of Central Florida2, UCL Institute of Child Health3, University of Cologne4, Columbia University Medical Center5, Harvard University6, French Institute of Health and Medical Research7, University of Utah8, Children's Hospital of Philadelphia9, University of Wisconsin-Madison10, Boston Children's Hospital11, University of Freiburg12, University of Texas Southwestern Medical Center13, Johns Hopkins University14, Newcastle University15, Karolinska Institutet16
TL;DR: The methods used to achieve these recommendations are presented, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management are presented.
TL;DR: In this paper, the physical origins and properties of π interactions are explained and their effects on molecular binding and chemical transformations are investigated, which offers opportunities for rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.
Abstract: Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.