Showing papers by "University of New Mexico 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
University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, International Centre for Diarrhoeal Disease Research, Bangladesh11, Centers for Disease Control and Prevention12, Tribhuvan University13, University of Bergen14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
1,470 citations
TL;DR: An updated comprehensive map of molecular targets of approved drugs is presented and the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes are explored.
Abstract: The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development. Here, we present an updated comprehensive map of molecular targets of approved drugs. We curate a total of 893 human and pathogen-derived biomolecules through which 1,578 US FDA-approved drugs act. These biomolecules include 667 human-genome-derived proteins targeted by drugs for human disease. Analysis of these drug targets indicates the continued dominance of privileged target families across disease areas, but also the growth of novel first-in-class mechanisms, particularly in oncology. We explore the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes. Through the collaboration of three independent teams, we highlight some of the ongoing challenges in accurately defining the targets of molecular therapeutics and present conventions for deconvoluting the complexities of molecular pharmacology and drug efficacy.
1,465 citations
TL;DR: The development of the concept of microbial fuel cell into a wider range of derivative technologies, called bioelectrochemical systems, is described, introducing briefly microbial electrolysis cells, microbial desalination cells and microbial electrosynthesis cells.
1,180 citations
University of South Carolina1, Los Alamos National Laboratory2, Moscow State University3, Delhi Technological University4, University of Paris5, University of California, Davis6, Indian Institute of Technology (BHU) Varanasi7, University of Moratuwa8, University of Illinois at Urbana–Champaign9, California Polytechnic State University10, Sandia National Laboratories11, Max Planck Society12, Indian Institute of Technology Kharagpur13, French Institute for Research in Computer Science and Automation14, University of New Mexico15, Charles University in Prague16, Birla Institute of Technology and Science17, Indian Institute of Technology Bombay18, University of West Bohemia19
TL;DR: The architecture of SymPy is presented, a description of its features, and a discussion of select domain specific submodules are discussed, to become the standard symbolic library for the scientific Python ecosystem.
Abstract: SymPy is an open source computer algebra system written in pure Python. It is built with a focus on extensibility and ease of use, through both interactive and programmatic applications. These characteristics have led SymPy to become a popular symbolic library for the scientific Python ecosystem. This paper presents the architecture of SymPy, a description of its features, and a discussion of select submodules. The supplementary material provide additional examples and further outline details of the architecture and features of SymPy.
1,126 citations
Cornell University1, Paris Descartes University2, University of Massachusetts Medical School3, Spanish National Research Council4, University of Rome Tor Vergata5, Boston Children's Hospital6, University of Pittsburgh7, National University of Cuyo8, National Scientific and Technical Research Council9, Albert Einstein College of Medicine10, University of California, San Francisco11, University of New Mexico12, Goethe University Frankfurt13, University of Split14, University of Helsinki15, University of Salento16, German Cancer Research Center17, Virginia Commonwealth University18, St. Jude Children's Research Hospital19, Discovery Institute20, Harvard University21, University of Tromsø22, Hungarian Academy of Sciences23, Eötvös Loránd University24, New York University25, University of Vienna26, Babraham Institute27, University of South Australia28, University of Texas Southwestern Medical Center29, Howard Hughes Medical Institute30, University of Oviedo31, University of Graz32, National Institutes of Health33, Queens College34, City University of New York35, University of Tokyo36, University of Zurich37, Novartis38, Austrian Academy of Sciences39, University of Groningen40, University of Cambridge41, University of Padua42, University of Oxford43, University of Bern44, University of Oslo45, Foundation for Research & Technology – Hellas46, University of Crete47, Francis Crick Institute48, Osaka University49, Icahn School of Medicine at Mount Sinai50
TL;DR: A panel of leading experts in the field attempts here to define several autophagy‐related terms based on specific biochemical features to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagic research.
Abstract: Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.
1,095 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.
1,014 citations
TL;DR: This study demonstrates how atomically dispersed ionic platinum (Pt2+) on ceria (CeO2), which is already thermally stable, can be activated via steam treatment to simultaneously achieve the goals of low-temperature carbon monoxide (CO) oxidation activity while providing outstanding hydrothermal stability.
Abstract: To improve fuel efficiency, advanced combustion engines are being designed to minimize the amount of heat wasted in the exhaust. Hence, future generations of catalysts must perform at temperatures that are 100°C lower than current exhaust-treatment catalysts. Achieving low-temperature activity, while surviving the harsh conditions encountered at high engine loads, remains a formidable challenge. In this study, we demonstrate how atomically dispersed ionic platinum (Pt2+) on ceria (CeO2), which is already thermally stable, can be activated via steam treatment (at 750°C) to simultaneously achieve the goals of low-temperature carbon monoxide (CO) oxidation activity while providing outstanding hydrothermal stability. A new type of active site is created on CeO2 in the vicinity of Pt2+, which provides the improved reactivity. These active sites are stable up to 800°C in oxidizing environments.
1,003 citations
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
730 citations
TL;DR: There is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders, however, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper.
699 citations
Oklahoma State University–Stillwater1, University of Sydney2, Macquarie University3, 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, United States Forest Service22, Northern Arizona University23, 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.
National Institutes of Health1, University of Texas Southwestern Medical Center2, University of Alabama at Birmingham3, Ohio State University4, Primary Children's Hospital5, University of Florida6, University of New Mexico7, New York University8, University of Virginia9, Seattle Cancer Care Alliance10, University of California, San Francisco11, University of Pennsylvania12
TL;DR: Using integrated genomic analysis of 264 T-ALL cases, 106 putative driver genes are identified and new mechanisms of coding and noncoding alteration are described, which suggests that different signaling pathways have distinct roles according to maturational stage.
Abstract: Genetic alterations that activate NOTCH1 signaling and T cell transcription factors, coupled with inactivation of the INK4/ARF tumor suppressors, are hallmarks of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out. Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, half of which had not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 and MYCN). We describe new mechanisms of coding and noncoding alteration and identify ten recurrently altered pathways, with associations between mutated genes and pathways, and stage or subtype of T-ALL. For example, NRAS/FLT3 mutations were associated with immature T-ALL, JAK3/STAT5B mutations in HOXA1 deregulated ALL, PTPN2 mutations in TLX1 deregulated T-ALL, and PIK3R1/PTEN mutations in TAL1 deregulated ALL, which suggests that different signaling pathways have distinct roles according to maturational stage. This genomic landscape provides a logical framework for the development of faithful genetic models and new therapeutic approaches.
Woods Hole Research Center1, Northern Arizona University2, University of Utah3, Carnegie Institution for Science4, California Institute of Technology5, University of Nevada, Reno6, University of New Mexico7, United States Forest Service8, Princeton University9, Oak Ridge National Laboratory10, University of Maine11, Pacific Northwest National Laboratory12, University of Illinois at Urbana–Champaign13, Auburn University14
TL;DR: This analysis of three independent datasets of gross primary productivity shows that, across diverse ecosystems, drought recovery times are strongly associated with climate and carbon cycle dynamics, with biodiversity and CO2 fertilization as secondary factors.
Abstract: Drought, a recurring phenomenon with major impacts on both human and natural systems, is the most widespread climatic extreme that negatively affects the land carbon sink. Although twentieth-century trends in drought regimes are ambiguous, across many regions more frequent and severe droughts are expected in the twenty-first century. Recovery time-how long an ecosystem requires to revert to its pre-drought functional state-is a critical metric of drought impact. Yet the factors influencing drought recovery and its spatiotemporal patterns at the global scale are largely unknown. Here we analyse three independent datasets of gross primary productivity and show that, across diverse ecosystems, drought recovery times are strongly associated with climate and carbon cycle dynamics, with biodiversity and CO2 fertilization as secondary factors. Our analysis also provides two key insights into the spatiotemporal patterns of drought recovery time: first, that recovery is longest in the tropics and high northern latitudes (both vulnerable areas of Earth's climate system) and second, that drought impacts (assessed using the area of ecosystems actively recovering and time to recovery) have increased over the twentieth century. If droughts become more frequent, as expected, the time between droughts may become shorter than drought recovery time, leading to permanently damaged ecosystems and widespread degradation of the land carbon sink.
TL;DR: This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data.
Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...
Wellcome Trust Sanger Institute1, Haukeland University Hospital2, University of Bergen3, University of Oxford4, University of Cambridge5, European Bioinformatics Institute6, Los Alamos National Laboratory7, University of New Mexico8, Francis Crick Institute9, Katholieke Universiteit Leuven10, Memorial Sloan Kettering Cancer Center11, King's College London12, Université libre de Bruxelles13, Erasmus University Medical Center14, Brigham and Women's Hospital15, Harvard University16, Institute of Cancer Research17
TL;DR: Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor.
TL;DR: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems and should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.
TL;DR: It is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse, but once initiated, both medications were equally safe and effective.
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TL;DR: The white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.
Abstract: This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.
TL;DR: Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS and is exploited to apply a local energy calibration and corrections depending on the nature of the cluster.
Abstract: The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.
TL;DR: This work identifies four key issues that present challenges to understanding and classifying mental disorder and discusses how the three systems’ approaches to these key issues correspond or diverge as a result of their different histories, purposes, and constituencies.
Abstract: The diagnosis of mental disorder initially appears relatively straightforward: Patients present with symptoms or visible signs of illness; health professionals make diagnoses based primarily on these symptoms and signs; and they prescribe medication, psychotherapy, or both, accordingly. However, despite a dramatic expansion of knowledge about mental disorders during the past half century, understanding of their components and processes remains rudimentary. We provide histories and descriptions of three systems with different purposes relevant to understanding and classifying mental disorder. Two major diagnostic manuals-the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders-provide classification systems relevant to public health, clinical diagnosis, service provision, and specific research applications, the former internationally and the latter primarily for the United States. In contrast, the National Institute of Mental Health's Research Domain Criteria provides a framework that emphasizes integration of basic behavioral and neuroscience research to deepen the understanding of mental disorder. We identify four key issues that present challenges to understanding and classifying mental disorder: etiology, including the multiple causality of mental disorder; whether the relevant phenomena are discrete categories or dimensions; thresholds, which set the boundaries between disorder and nondisorder; and comorbidity, the fact that individuals with mental illness often meet diagnostic requirements for multiple conditions. We discuss how the three systems' approaches to these key issues correspond or diverge as a result of their different histories, purposes, and constituencies. Although the systems have varying degrees of overlap and distinguishing features, they share the goal of reducing the burden of suffering due to mental disorder.
TL;DR: How cognitive flexibility is measured by reversal learning is described and new definitions of the construct validity of the task are discussed that are serving as a heuristic to guide future research in this field.
TL;DR: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay, and data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients.
TL;DR: Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults.
Abstract: BackgroundObesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia MethodsIn this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss Participants were randomly assigned to a weight-management program plus one of three exercise programs — aerobic training, resistance training, or combined aerobic and resistance training — or to a control group (no weight-management or exercise program) The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance) Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions ResultsA total of 141 participants completed the study The Physical Performa
TL;DR: The Pierre Auger Collaboration reports the observation of thousands of cosmic rays with ultrahigh energies of several exa–electron volts, arriving in a slightly dipolar distribution, showing that they originate outside the Milky Way Galaxy.
Abstract: Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature Clues to their origin come from studying the distribution of their arrival directions Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km 2 sr year, we determined the existence of anisotropy in arrival directions The anisotropy, detected at more than a 52σ level of significance, can be described by a dipole with an amplitude of 65 − 09 + 13 percent toward right ascension α d = 100 ± 10 degrees and declination δ d = − 24 − 13 + 12 degrees That direction indicates an extragalactic origin for these ultrahigh-energy particles
University of Utah1, Los Alamos National Laboratory2, National Autonomous University of Mexico3, Universidad Michoacana de San Nicolás de Hidalgo4, Michigan Technological University5, Polytechnic University of Puerto Rico6, University of Rochester7, University of Maryland, College Park8, University of Wisconsin-Madison9, National Institute of Astrophysics, Optics and Electronics10, Max Planck Society11, Polish Academy of Sciences12, Benemérita Universidad Autónoma de Puebla13, University of Guadalajara14, George Mason University15, Marshall Space Flight Center16, University of New Mexico17, Georgia Institute of Technology18, Michigan State University19, Instituto Politécnico Nacional20, Pennsylvania State University21, Universidad Autónoma del Estado de Hidalgo22, Santa Cruz Institute for Particle Physics23, Stanford University24, University of California, Irvine25
TL;DR: In this paper, the authors reported the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14).
Abstract: The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera–electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera–electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.
McMaster University1, University of Calgary2, Geneva College3, University of Oslo4, Aarhus University Hospital5, University of Oxford6, University of Western Ontario7, University of Toronto8, McGill University9, Dalhousie University10, Columbia University11, Katholieke Universiteit Leuven12, Aarhus University13, University of Hong Kong14, Henry Ford Hospital15, Post Graduate Institute of Medical Education and Research16, Mayo Clinic17, Shanghai Jiao Tong University18, University of California19, University of New Mexico20, Universidade de Pernambuco21, University of Sheffield22, University of Pisa23, Yale University24, University of Victoria25, Harvard University26, University of Florence27
TL;DR: The current state of the art in the diagnosis and management ofPHPT is presented and the Canadian Position paper on PHPT is updated and an overview of the impact of PHPT on the skeleton and other target organs is presented.
Abstract: The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.
TL;DR: In this article, a search for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states was conducted using 36 : 1 fb(-1) of proton-proton collision data.
Abstract: A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root ...
Catherine M. Phelan, Karoline Kuchenbaecker1, Karoline Kuchenbaecker2, Jonathan Tyrer1 +440 more•Institutions (156)
TL;DR: Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
TL;DR: Advice is provided regarding core communication skills and tasks that apply across the continuum of cancer care, such as discussion of goals of care and prognosis, treatment selection, end-of-life care, facilitating family involvement in care, and clinician training in communication skills.
Abstract: PurposeTo provide guidance to oncology clinicians on how to use effective communication to optimize the patient-clinician relationship, patient and clinician well-being, and family well-being.MethodsASCO convened a multidisciplinary panel of medical oncology, psychiatry, nursing, hospice and palliative medicine, communication skills, health disparities, and advocacy experts to produce recommendations. Guideline development involved a systematic review of the literature and a formal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, and randomized controlled trials published from 2006 through October 1, 2016.ResultsThe systematic review included 47 publications. With the exception of clinician training in communication skills, evidence for many of the clinical questions was limited. Draft recommendations underwent two rounds of consensus voting before being finalized.RecommendationsIn addition to providing guidance regarding core communication skills and t...
TL;DR: Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome, and trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph- like ALL.
Abstract: Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.