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Showing papers by "Case Western Reserve University published in 2015"


Journal ArticleDOI
Mohsen Naghavi1, Haidong Wang1, Rafael Lozano1, Adrian Davis2  +728 moreInstitutions (294)
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.

5,792 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

5,668 citations


Journal ArticleDOI
Theo Vos1, Ryan M Barber1, Brad Bell1, Amelia Bertozzi-Villa1  +686 moreInstitutions (287)
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.

4,510 citations


Journal ArticleDOI
TL;DR: In this article, the most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain, and the authors propose a target of less than 120 mm Hg.
Abstract: BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).

4,125 citations


Journal ArticleDOI
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

3,947 citations


Journal ArticleDOI
TL;DR: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrogram, and a novel optical interferometer.
Abstract: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 sq. deg of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-Object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include measured abundances of 15 different elements for each star. In total, SDSS-III added 2350 sq. deg of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 sq. deg; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5,513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.

2,471 citations


Journal ArticleDOI
Christina Fitzmaurice1, Christina Fitzmaurice2, Daniel Dicker1, Daniel Dicker2, Amanda W Pain1, Hannah Hamavid1, Maziar Moradi-Lakeh1, Michael F. MacIntyre3, Michael F. MacIntyre1, Christine Allen1, Gillian M. Hansen1, Rachel Woodbrook1, Charles D.A. Wolfe1, Randah R. Hamadeh4, Ami R. Moore5, A. Werdecker6, Bradford D. Gessner, Braden Te Ao, Brian J. McMahon7, Chante Karimkhani8, Chuanhua Yu9, Graham S Cooke10, David C. Schwebel11, David O. Carpenter12, David M. Pereira13, Denis Nash, Dhruv S. Kazi14, Diego De Leo15, Dietrich Plass16, Kingsley N. Ukwaja17, George D. Thurston, Kim Yun Jin18, Edgar P. Simard19, Edward J Mills20, Eun-Kee Park21, Ferrán Catalá-López22, Gabrielle deVeber, Carolyn C. Gotay23, Gulfaraz Khan24, H. Dean Hosgood25, Itamar S. Santos26, Janet L Leasher27, Jasvinder A. Singh28, James Leigh12, Jost B. Jonas29, Juan R. Sanabria30, Justin Beardsley31, Justin Beardsley32, Kathryn H. Jacobsen33, Ken Takahashi34, Richard C. Franklin, Luca Ronfani35, Marcella Montico36, Luigi Naldi36, Marcello Tonelli, Johanna M. Geleijnse37, Max Petzold38, Mark G. Shrime39, Mark G. Shrime40, Mustafa Z. Younis41, Naohiro Yonemoto42, Nicholas J K Breitborde, Paul S. F. Yip43, Farshad Pourmalek44, Paulo A. Lotufo24, Alireza Esteghamati27, Graeme J. Hankey45, Raghib Ali46, Raimundas Lunevicius33, Reza Malekzadeh47, Robert P. Dellavalle45, Robert G. Weintraub48, Robert G. Weintraub49, Robyn M. Lucas50, Robyn M. Lucas51, Roderick J Hay52, David Rojas-Rueda, Ronny Westerman, Sadaf G. Sepanlou53, Sandra Nolte, Scott B. Patten54, Scott Weichenthal37, Semaw Ferede Abera55, Seyed-Mohammad Fereshtehnejad56, Ivy Shiue57, Tim Driscoll58, Tim Driscoll59, Tommi J. Vasankari29, Ubai Alsharif, Vafa Rahimi-Movaghar54, Vasiliy Victorovich Vlassov45, W. S. Marcenes60, Wubegzier Mekonnen61, Yohannes Adama Melaku62, Yuichiro Yano56, Al Artaman63, Ismael Campos, Jennifer H MacLachlan41, Ulrich O Mueller, Daniel Kim53, Matias Trillini64, Babak Eshrati65, Hywel C Williams66, Kenji Shibuya67, Rakhi Dandona68, Kinnari S. Murthy69, Benjamin C Cowie69, Azmeraw T. Amare, Carl Abelardo T. Antonio70, Carlos A Castañeda-Orjuela71, Coen H. Van Gool, Francesco Saverio Violante, In-Hwan Oh72, Kedede Deribe73, Kjetil Søreide62, Kjetil Søreide74, Luke D. Knibbs75, Luke D. Knibbs76, Maia Kereselidze77, Mark Green78, Rosario Cardenas79, Nobhojit Roy80, Taavi Tillmann57, Yongmei Li81, Hans Krueger82, Lorenzo Monasta24, Subhojit Dey36, Sara Sheikhbahaei, Nima Hafezi-Nejad45, G Anil Kumar45, Chandrashekhar T Sreeramareddy69, Lalit Dandona83, Haidong Wang1, Haidong Wang69, Stein Emil Vollset1, Ali Mokdad84, Ali Mokdad75, Joshua A. Salomon1, Rafael Lozano41, Theo Vos1, Mohammad H. Forouzanfar1, Alan D. Lopez1, Christopher J L Murray50, Mohsen Naghavi1 
Institute for Health Metrics and Evaluation1, University of Washington2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Cancer Treatment Centers of America31, Case Western Reserve University32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of the Witwatersrand39, University of Gothenburg40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, Veterans Health Administration48, University of Colorado Denver49, University of Melbourne50, Royal Children's Hospital51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, University of Edinburgh58, Northumbria University59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, University of Bergen75, Stavanger University Hospital76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

2,375 citations


Journal ArticleDOI
TL;DR: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.
Abstract: BACKGROUND Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. RESULTS A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. CONCLUSIONS Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.)

2,009 citations


Journal ArticleDOI
TL;DR: This paper presents a probabilistic procedure for estimating the polymethine content of carbon dioxide using a straightforward two-step procedure, and shows good results in both the stationary and the liquid phase.
Abstract: Liming Dai,*,†,‡ Yuhua Xue,†,‡ Liangti Qu,* Hyun-Jung Choi, and Jong-Beom Baek* †Center of Advanced Science and Engineering for Carbon (Case4Carbon), Department of Macromolecular Science and Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States Key Laboratory of Cluster Science, Ministry of Education of China, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, Department of Chemistry, School of Science, Beijing Institute of Technology, Beijing 100081, People’s Republic of China School of Energy and Chemical Engineering/Center for Dimension-Controllable Covalent Organic Frameworks, Ulsan National Institute of Science and Technology (UNIST), 100 Banyeon, Ulsan, 689-798, South Korea

1,967 citations


Journal ArticleDOI
08 Sep 2015-JAMA
TL;DR: Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased.
Abstract: Importance Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. Objective To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers. Design, Setting, Participants Prospective registry of 34 636 infants, 22 to 28 weeks’ gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. Exposures Extremely preterm birth. Main Outcomes and Measures Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. Results Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants];P Conclusions and Relevance Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks’ gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. Trial Registration clinicaltrials.gov Identifier:NCT00063063.

1,818 citations


29 Jan 2015
TL;DR: The current state of the genetic dissection of complex traits is summarized in this paper, which describes the methods, limitations, and recent applications to biological problems, including linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses.
Abstract: Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Geneticists have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits—describing the methods, limitations, and recent applications to biological problems.


Journal ArticleDOI
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.

Journal ArticleDOI
27 Aug 2015-Cell
TL;DR: In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.

Journal ArticleDOI
TL;DR: In this article, a catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory is presented, and the current understanding of the structure and dynamics of compact objects in these theories is summarized.
Abstract: One century after its formulation, Einstein's general relativity (GR) has made remarkable predictions and turned out to be compatible with all experimental tests. Most of these tests probe the theory in the weak-field regime, and there are theoretical and experimental reasons to believe that GR should be modified when gravitational fields are strong and spacetime curvature is large. The best astrophysical laboratories to probe strong-field gravity are black holes and neutron stars, whether isolated or in binary systems. We review the motivations to consider extensions of GR. We present a (necessarily incomplete) catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory, and we summarize our current understanding of the structure and dynamics of compact objects in these theories. We discuss current bounds on modified gravity from binary pulsar and cosmological observations, and we highlight the potential of future gravitational wave measurements to inform us on the behavior of gravity in the strong-field regime.

Journal ArticleDOI
12 Mar 2015-Cell
TL;DR: It is shown that optimal codon content accounts for the similar stabilities observed in mRNAs encoding proteins with coordinated physiological function, demonstrating that codon optimization exists as a mechanism to finely tune levels of m RNAs and, ultimately, proteins.

Journal ArticleDOI
TL;DR: A 3D N-doped graphene foam with a 6.8 at% nitrogen content is used as an anode in sodium ion batteries to deliver a high initial reversible capacity with a long-term retention of 69.7% after 150 cycles.
Abstract: A 3D N-doped graphene foam with a 6.8 at% nitrogen content is prepared by annealing a freeze-dried graphene oxide foam in ammonia. It is used as an anode in sodium ion batteries to deliver a high initial reversible capacity of 852.6 mA h g(-1) at 1 C between 0.02 and 3 V with a long-term retention of 69.7% after 150 cycles.

Journal ArticleDOI
TL;DR: The high costs associated with cancer care have created a difficult situation for patients and the oncologists who care for them and will require greater understanding of all the risks and benefits of various treatment options as well as the consequences of specific choices.
Abstract: Health care costs in the United States present a major challenge to the national economic well being. The Centers for Medicare and Medicaid Services (CMS) has projected that US health care spending will reach $4.3 trillion and account for 19.3% of the national gross domestic product by 2019.1 This growth in spending—both in absolute terms and as a proportion of our gross domestic product—has not been accompanied by commensurate improvements in health outcomes, despite expenditures far exceeding those of other countries.2–4 One of the fastest growing components of US health care costs is cancer care, the cost of which is now estimated to increase from $125 billion in 2010 to $158 billion in 2020.1 Although cancer care represents a small fraction of overall health care costs, its contribution to health care cost escalation is increasing faster than those of most other areas because of several factors: the increasing prevalence of cancer due to the overall aging of the population and better control of some causes of competing mortality; the introduction of costly new drugs and techniques in radiation therapy and surgery; and the adoption of more expensive diagnostic tests. In some cases, the adoption of newer, more expensive diagnostic and therapeutic interventions may not be well supported by medical evidence, thereby raising costs without improving outcomes.5 Coupled with, or even driving, some of these rising costs are sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.6 Historically, most individuals in the United States were shielded from the acute economic impact of expensive care because they had health insurance. However, current trends suggest that patients will find themselves increasingly responsible for a greater proportion of the cost of their health care. Cost shifting or sharing can occur through the increased use of high-deductible policies and larger copayments. These increased costs are already commonplace and may not be affordable for many families. Indeed, health care expenditures are cited as a major cause of personal bankruptcy,7 and the term financial toxicity has entered the vernacular as a means of describing the financial distress that now often accompanies cancer treatment.8 Like other toxicities of cancer treatment, financial toxicity resulting from out-of-pocket treatment expenses can reduce quality of life and impede delivery of high-quality care.9,10 Patients experiencing high out-of-pocket costs have reported reducing their spending on food and clothing, reducing the frequency with which they take prescribed medications, avoiding recommended procedures, and skipping physician appointments to save money.10,11 These unintended consequences risk an increase in health disparities, which runs counter to some of the key goals of health care reform. In many communities, the high costs associated with cancer care have created a difficult situation for patients and the oncologists who care for them. Addressing this situation will require greater understanding of all the risks and benefits of various treatment options as well as the consequences of specific choices. In this regard, studies have shown that patients specifically want financial information about treatment alternatives along with information about medical effectiveness and treatment toxicity. However, they often do not receive it. Closing this knowledge gap will require educated providers who are able to sensitively initiate a dialogue about the cost of care with their patients when appropriate.12,13 Patients with cancer are often surprised by and unprepared for the high out-of-pocket costs of treatments. They also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all. Oncologists are generally aware of this conundrum but uncertain about whether and how the cost of care should affect their recommendations.14 Although raising awareness of costs and providing tools to assess value may help to manage costs while maintaining high-quality care, some oncologists see this as being in conflict with their duty to individual patients.15 Recent American Society of Clinical Oncology Efforts Motivated by our responsibility to help oncologists deliver the highest-quality care to patients everywhere, the American Society of Clinical Oncology (ASCO) formed the Task Force on the Cost of Cancer Care in 2007. Its mission includes educating oncologists about the importance of discussing costs associated with recommended treatments, empowering patients to ask questions pertaining to the anticipated costs of their treatment options, identifying the drivers of the rising costs of cancer care, and ultimately developing policy positions that will help Americans move toward more equal access to the highest-quality care at the lowest cost.16 In 2012, through the work of the Task Force, ASCO responded to the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation and identified specific instances of overuse in the delivery of cancer care. ASCO used a deliberative consensus process to identify five common clinical practices that are not supported by high-level evidence. A second list of five was developed using the same process and submitted to the Choosing Wisely Campaign in 2013. ASCO amplified the evidence basis for both top-five lists in two publications17,18 and is now developing measures to evaluate the use of these practices as part of its Quality Oncology Practice Initiative. These exercises have provided opportunities to develop a rigorous but flexible approach to assessing efficacy across diagnostic and treatment domains.

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TL;DR: This paper presents a poster presented at the 2016 American Academy of Gastroenterology and Hepatology Congress, presenting a poster entitled “Advances in GastroEnterology-Hepatology: Foundations of Drug Discovery and Administration, 2nd Ed.”

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TL;DR: A combined optical and electrical transport study on the many-body collective-order phase diagram of NbSe2 down to a thickness of one monolayer opens up a new window for search and control of collective phases of two-dimensional matter, as well as expanding the functionalities of these materials for electronic applications.
Abstract: Enhanced electron–phonon interactions in mono- and few-layer NbSe2 result in a significantly increased transition temperature of charge density waves compared with values in the bulk.

Journal ArticleDOI
TL;DR: It is demonstrated that GSCs secrete periostin (POSTN) to recruit TAMs and found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood.
Abstract: Bao and colleagues report that glioblastoma cancer stem cells produce periostin, which in turn recruits tumour-associated macrophages to the tumour site to foster growth.

Journal ArticleDOI
A. Aab1, P. Abreu2, Marco Aglietta3, Marco Aglietta4  +640 moreInstitutions (64)
TL;DR: The Pierre Auger Observatory as mentioned in this paper, the world's largest cosmic ray observatory, has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr.
Abstract: The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above $10^{17}$ eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water-Cherenkov particle detector stations spread over 3000 km$^2$ overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km$^2$, 61 detector infill array. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Auger Observatory.

Journal ArticleDOI
Lindsey Bleem1, Lindsey Bleem2, B. Stalder3, T. de Haan4, K. A. Aird2, Steven W. Allen5, Steven W. Allen6, Douglas Applegate, Matthew L. N. Ashby3, Mark W. Bautz7, Matthew B. Bayliss3, Bradford Benson8, Bradford Benson2, Sebastian Bocquet9, Mark Brodwin10, John E. Carlstrom, C. L. Chang2, C. L. Chang1, I-Non Chiu9, Hsiao-Mei Cho11, Alejandro Clocchiatti12, T. M. Crawford2, A. T. Crites13, A. T. Crites2, Shantanu Desai9, J. P. Dietrich9, Matt Dobbs4, Matt Dobbs14, R. J. Foley3, R. J. Foley15, William R. Forman3, Elizabeth George16, Michael D. Gladders2, Anthony H. Gonzalez17, N. W. Halverson18, C. Hennig9, Henk Hoekstra19, Gilbert Holder4, W. L. Holzapfel20, J. D. Hrubes2, Christine Jones3, Ryan Keisler5, Ryan Keisler2, Lloyd Knox21, Adrian T. Lee20, Adrian T. Lee22, E. M. Leitch2, Jiayi Liu9, M. Lueker13, M. Lueker20, Daniel M. Luong-Van2, Adam Mantz, Daniel P. Marrone23, Michael McDonald7, Jeff McMahon24, S. S. Meyer2, L. M. Mocanu2, Joseph J. Mohr16, S. S. Murray3, Stephen Padin2, Stephen Padin13, C. Pryke25, Christian L. Reichardt26, Christian L. Reichardt20, Armin Rest27, Jonathan Ruel3, J. E. Ruhl28, Benjamin Saliwanchik28, A. Saro9, J. T. Sayre28, K. K. Schaffer2, K. K. Schaffer29, Tim Schrabback, Erik Shirokoff20, Erik Shirokoff13, Jizhou Song24, Jizhou Song30, Helmuth Spieler22, Spencer A. Stanford31, Spencer A. Stanford21, Z. K. Staniszewski13, Z. K. Staniszewski28, Antony A. Stark3, K. T. Story2, Christopher W. Stubbs3, K. Vanderlinde32, Joaquin Vieira15, Alexey Vikhlinin3, R. Williamson2, R. Williamson13, Oliver Zahn20, Oliver Zahn22, A. Zenteno9 
TL;DR: In this article, the authors presented a catalog of galaxy clusters selected via their Sunyaev-Zel'dovich (SZ) effect signature from 2500 deg^2 of South Pole Telescope (SPT) data.
Abstract: We present a catalog of galaxy clusters selected via their Sunyaev-Zel'dovich (SZ) effect signature from 2500 deg^2 of South Pole Telescope (SPT) data. This work represents the complete sample of clusters detected at high significance in the 2500 deg^2 SPT-SZ survey, which was completed in 2011. A total of 677 (409) cluster candidates are identified above a signal-to-noise threshold of ξ = 4.5 (5.0). Ground- and space-based optical and near-infrared (NIR) imaging confirms overdensities of similarly colored galaxies in the direction of 516 (or 76%) of the ξ > 4.5 candidates and 387 (or 95%) of the ξ > 5 candidates; the measured purity is consistent with expectations from simulations. Of these confirmed clusters, 415 were first identified in SPT data, including 251 new discoveries reported in this work. We estimate photometric redshifts for all candidates with identified optical and/or NIR counterparts; we additionally report redshifts derived from spectroscopic observations for 141 of these systems. The mass threshold of the catalog is roughly independent of redshift above z ~ 0.25 leading to a sample of massive clusters that extends to high redshift. The median mass of the sample is M_(500c(ρcrit)) ~ 3.5 x 10^(14)M_☉ h_(70)^(-1), the median redshift is z_(med) = 0.55, and the highest-redshift systems are at z > 1.4. The combination of large redshift extent, clean selection, and high typical mass makes this cluster sample of particular interest for cosmological analyses and studies of cluster formation and evolution.

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TL;DR: In this paper, the authors measured the distribution of stars in the [/Fe] versus [Fe/H] plane and the metallicity distribution functions (MDFs) across an unprecedented volume of the Milky Way disk, with radius 3 < R < 15 kpc and height kpc.
Abstract: Using a sample of 69,919 red giants from the SDSS-III/APOGEE Data Release 12, we measure the distribution of stars in the [/Fe] versus [Fe/H] plane and the metallicity distribution functions (MDFs) across an unprecedented volume of the Milky Way disk, with radius 3 < R < 15 kpc and height kpc. Stars in the inner disk (R < 5 kpc) lie along a single track in [/Fe] versus [Fe/H], starting with -enhanced, metal-poor stars and ending at [/Fe] ∼ 0 and [Fe/H] ∼ +0.4. At larger radii we find two distinct sequences in [/Fe] versus [Fe/H] space, with a roughly solar- sequence that spans a decade in metallicity and a high- sequence that merges with the low- sequence at super-solar [Fe/H]. The location of the high- sequence is nearly constant across the disk.

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TL;DR: It is shown that TREM2 deficiency reduces the number of macrophages infiltrating the brain and is protective against disease pathogenesis in mouse models of Alzheimer’s disease.
Abstract: Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2's involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45(hi)Ly6C(+) myeloid cells, but not on P2RY12(+) parenchymal microglia. In AD mice deficient for TREM2, the CD45(hi)Ly6C(+) macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2(+) macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

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TL;DR: A critical review on the recent advances in carbon-based metal-free catalysts for fuel cells and metal-air batteries, and discusses the perspectives and challenges in this rapidly developing field of practical significance.
Abstract: Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) play curial roles in electrochemical energy conversion and storage, including fuel cells and metal-air batteries. Having rich multidimensional nanoarchitectures [for example, zero-dimensional (0D) fullerenes, 1D carbon nanotubes, 2D graphene, and 3D graphite] with tunable electronic and surface characteristics, various carbon nanomaterials have been demonstrated to act as efficient metal-free electrocatalysts for ORR and OER in fuel cells and batteries. We present a critical review on the recent advances in carbon-based metal-free catalysts for fuel cells and metal-air batteries, and discuss the perspectives and challenges in this rapidly developing field of practical significance.

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TL;DR: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients.
Abstract: BackgroundBetween-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. MethodsWe studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). ResultsOverall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and su...

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TL;DR: In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy were similar to those after a longer course of antibiotics that extended until after the resolution of physiological abnormalities.
Abstract: Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, −0.5 percentage point; 95% confidence interval [CI], −7.0 to 8.0; P = 0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, −4.0 days; 95% CI, −4.7 to −3.3; P<0.001). No signifi cant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes. CONCLUSIONS In patients with intraabdominal infections who had undergone an adequate sourcecontrol procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials .gov number, NCT00657566.)

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TL;DR: In this paper, a new class of heteroatom-doped metal-free carbon catalysts has been developed, which, as alternative ORR catalysts, could dramatically reduce the cost and increase the efficiency of fuel cells and metal-air batteries.
Abstract: The oxygen reduction reaction (ORR) plays an important role in renewable energy technologies, such as fuel cells and metal–air batteries. Along with the extensive research and development of nonprecious metal catalysts (NPMCs) to reduce/replace Pt for electrocatalytic reduction of oxygen, a new class of heteroatom-doped metal-free carbon catalysts has been recently developed, which, as alternative ORR catalysts, could dramatically reduce the cost and increase the efficiency of fuel cells and metal–air batteries. The improved catalytic performance of heteroatom-doped carbon ORR catalysts has been attributed to the doping-induced charge redistribution around the heteroatom dopants, which lowered the ORR potential and changed the O2 chemisorption mode to effectively weaken the O–O bonding, facilitating ORR at the heteroatom-doped carbon electrodes. Subsequently, this new metal-free ORR mechanism was confirmed by numerous studies, and the same principle has been applied to the development of various other eff...

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TL;DR: Key issues in interpreting (13)C metabolite labeling patterns are reviewed, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.