Showing papers by "Ohio State University published in 2015"
TL;DR: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.
Abstract: BackgroundSomatic mutations have the potential to encode “non-self” immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. MethodsWe conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti–programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair–deficient colorectal cancers, patients with mismatch repair–proficient colorectal cancers, and patients with mismatch repair–deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. ResultsThe immune-related objective response rate and immune-related progression-free survival ...
6,835 citations
TL;DR: It is found that the diffusion lengths in CH3NH3PbI3 single crystals grown by a solution-growth method can exceed 175 micrometers under 1 sun (100 mW cm−2) illumination and exceed 3 millimeters under weak light for both electrons and holes.
Abstract: Long, balanced electron and hole diffusion lengths greater than 100 nanometers in the polycrystalline organolead trihalide compound CH3NH3PbI3 are critical for highly efficient perovskite solar cells. We found that the diffusion lengths in CH3NH3PbI3 single crystals grown by a solution-growth method can exceed 175 micrometers under 1 sun (100 mW cm(-2)) illumination and exceed 3 millimeters under weak light for both electrons and holes. The internal quantum efficiencies approach 100% in 3-millimeter-thick single-crystal perovskite solar cells under weak light. These long diffusion lengths result from greater carrier mobility, longer lifetime, and much smaller trap densities in the single crystals than in polycrystalline thin films. The long carrier diffusion lengths enabled the use of CH3NH3PbI3 in radiation sensing and energy harvesting through the gammavoltaic effect, with an efficiency of 3.9% measured with an intense cesium-137 source.
4,393 citations
Shadab Alam1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto4 +360 more•Institutions (102)
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
TL;DR: This test can be used for models that integrate moderation and mediation in which the relationship between the indirect effect and the moderator is estimated as linear, including many of the models described by Edwards and Lambert (2007) and Preacher, Rucker, and Hayes (2007), as well as extensions of these models to processes involving multiple mediators operating in parallel or in serial.
Abstract: I describe a test of linear moderated mediation in path analysis based on an interval estimate of the parameter of a function linking the indirect effect to values of a moderator-a parameter that I call the index of moderated mediation. This test can be used for models that integrate moderation and mediation in which the relationship between the indirect effect and the moderator is estimated as linear, including many of the models described by Edwards and Lambert ( 2007 ) and Preacher, Rucker, and Hayes ( 2007 ) as well as extensions of these models to processes involving multiple mediators operating in parallel or in serial. Generalization of the method to latent variable models is straightforward. Three empirical examples describe the computation of the index and the test, and its implementation is illustrated using Mplus and the PROCESS macro for SPSS and SAS.
2,437 citations
TL;DR: A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided in this paper, covering approximately the last seven years, including developments in density functional theory and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces.
Abstract: A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Moller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr_2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.
2,396 citations
Emory University1, United States Environmental Protection Agency2, University of Iowa3, Case Western Reserve University4, University of Alabama at Birmingham5, Wayne State University6, Brown University7, Ohio State University8, Stanford University9, Lucile Packard Children's Hospital10, University of Texas Southwestern Medical Center11, RTI International12, Cincinnati Children's Hospital Medical Center13, Indiana University14, University of Texas Health Science Center at Houston15, Duke University16, University of New Mexico17, University of Rochester18, University of Pennsylvania19, Children's Mercy Hospital20, University of California, Los Angeles21, National Institutes of Health22
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
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
TL;DR: In this article, a sample of spectroscopically identified galaxies with z < 0.2 from the Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7), covering 6813 deg(2).
Abstract: We create a sample of spectroscopically identified galaxies with z < 0.2 from the Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7), covering 6813 deg(2). Galaxies are chosen to sample the highest mass haloes, with an effective bias of 1.5, allowing us to construct 1000 mock galaxy catalogues (described in Paper II), which we use to estimate statistical errors and test our methods. We use an estimate of the gravitational potential to 'reconstruct' the linear density fluctuations, enhancing the baryon acoustic oscillation (BAO) signal in the measured correlation function and power spectrum. Fitting to these measurements, we determine D-V(z(eff) = 0.15) = (664 +/- 25)(r(d)/r(d, fid)) Mpc; this is a better than 4 per cent distance measurement. This 'fills the gap' in BAO distance ladder between previously measured local and higher redshift measurements, and affords significant improvement in constraining the properties of dark energy. Combining our measurement with other BAO measurements from Baryon Oscillation Spectroscopic Survey and 6-degree Field Galaxy Redshift Survey galaxy samples provides a 15 per cent improvement in the determination of the equation of state of dark energy and the value of the Hubble parameter at z = 0 (H-0). Our measurement is fully consistent with the Planck results and the Lambda cold dark matter concordance cosmology, but increases the tension between Planck+BAO H-0 determinations and direct H-0 measurements.
1,566 citations
National Institutes of Health1, University of Toronto2, Martin Luther University of Halle-Wittenberg3, University of Pisa4, Medical College of Wisconsin5, Memorial Sloan Kettering Cancer Center6, Washington University in St. Louis7, University of Siena8, Heidelberg University9, University of Sydney10, University of Kentucky11, University of Naples Federico II12, Institut Gustave Roussy13, Ohio State University14
TL;DR: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC and developed 67 evidence-based recommendations to assist clinicians in the care of Patients with MTC.
Abstract: Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...
1,504 citations
Harvard University1, Kolling Institute of Medical Research2, University of Pennsylvania3, University of Pisa4, The Royal Marsden NHS Foundation Trust5, Ohio State University6, University of São Paulo7, University of California, Los Angeles8, Kobe University9, Oregon Health & Science University10, University of Ulsan11, Princess Margaret Cancer Centre12, Eisai13
TL;DR: Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer.
Abstract: Background Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131). Methods In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety. Results The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related. Conclusions Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131– refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.)
1,354 citations
Memorial Sloan Kettering Cancer Center1, Institut Gustave Roussy2, University of North Carolina at Chapel Hill3, Roswell Park Cancer Institute4, Vanderbilt University5, University of Rennes6, Ohio State University7, University of California, Davis8, Beth Israel Medical Center9, Lehigh Valley Hospital10, University Hospitals of Cleveland11, Providence Portland Medical Center12, University of Miami13, Ludwig Maximilian University of Munich14, Bristol-Myers Squibb15, Emory University16
TL;DR: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer and these data support the assessment of nivolumsab in randomised, controlled, phase 3 studies of first-line and second-line treatment.
Abstract: Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding Bristol-Myers Squibb.
TL;DR: Six new EBPs were identified in this review, and one EBP from the previous review was removed, and the authors discuss implications for current practices and future research.
Abstract: The purpose of this study was to identify evidenced-based, focused intervention practices for children and youth with autism spectrum disorder. This study was an extension and elaboration of a previous evidence-based practice review reported by Odom et al. (Prev Sch Fail 54:275–282, 2010b, doi:
10.1080/10459881003785506
). In the current study, a computer search initially yielded 29,105 articles, and the subsequent screening and evaluation process found 456 studies to meet inclusion and methodological criteria. From this set of research studies, the authors found 27 focused intervention practices that met the criteria for evidence-based practice (EBP). Six new EBPs were identified in this review, and one EBP from the previous review was removed. The authors discuss implications for current practices and future research.
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
SLAC National Accelerator Laboratory1, Stockholm University2, Santa Cruz Institute for Particle Physics3, Istituto Nazionale di Fisica Nucleare4, University of Wisconsin-Madison5, Goddard Space Flight Center6, University of Montpellier7, École Polytechnique8, INAF9, George Mason University10, University of Padua11, Instituto Politécnico Nacional12, Fermilab13, C. N. Yang Institute for Theoretical Physics14, Hiroshima University15, Paris Diderot University16, University of Göttingen17, University of North Florida18, University of Iceland19, Spanish National Research Council20, University of Maryland, College Park21, University of California, Irvine22, University of Denver23, Stony Brook University24, Texas A&M University25, Ohio State University26, United States Naval Research Laboratory27
TL;DR: In this article, the authors report on γ-ray observations of the Milky-Way satellite galaxies (dSphs) based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis.
Abstract: The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ≲100 GeV annihilating via quark and τ-lepton channels.
TL;DR: It was found that students in the gamified course showed less motivation, satisfaction, and empowerment over time than those in the non-gamified class, and some care should be taken when applying certain gamification mechanics to educational settings.
Abstract: Gamification, the application of game elements to non-game settings, continues to grow in popularity as a method to increase student engagement in the classroom. We tested students across two courses, measuring their motivation, social comparison, effort, satisfaction, learner empowerment, and academic performance at four points during a 16-week semester. One course received a gamified curriculum, featuring a leaderboard and badges, whereas the other course received the same curriculum without the gamified elements. Our results found that students in the gamified course showed less motivation, satisfaction, and empowerment over time than those in the non-gamified class. The effect of course type on students' final exam scores was mediated by students' levels of intrinsic motivation, with students in the gamified course showing less motivation and lower final exam scores than the non-gamified class. This suggests that some care should be taken when applying certain gamification mechanics to educational settings. Longitudinal study on effects of gamification in the classroom.71 students surveyed at four time points in gamified or non-gamified course.Over time, gamified students were less motivated, empowered, and satisfied.Gamified course negatively affected final exam grades through intrinsic motivation.Gamified systems strongly featuring rewards may have negative effects.
TL;DR: An empirical q-factor model consisting of the market factor, a size factor, an investment factor, and a profitability factor largely summarizes the cross section of average stock returns as mentioned in this paper, and with a few exceptions, the Q-Factor model's performance is at least comparable to, and in many cases better than that of the Fama-French (1993) 3 factor model and the Carhart (1997) 4 factor model in capturing the remaining significant anomalies.
Abstract: An empirical q-factor model consisting of the market factor, a size factor, an investment factor, and a profitability factor largely summarizes the cross section of average stock returns. A comprehensive examination of nearly 80 anomalies reveals that about one-half of the anomalies are insignificant in the broad cross section. More importantly, with a few exceptions, the q-factor model's performance is at least comparable to, and in many cases better than that of the Fama-French (1993) 3-factor model and the Carhart (1997) 4-factor model in capturing the remaining significant anomalies.
TL;DR: This work reconstructed 8 complete and 789 draft genomes from bacteria representing >35 phyla and documented features that consistently distinguish these organisms from other bacteria, infer that this group, which may comprise >15% of the bacterial domain, has shared evolutionary history, and describe it as the candidate phyla radiation (CPR).
Abstract: A prominent feature of the bacterial domain is a radiation of major lineages that are defined as candidate phyla because they lack isolated representatives. Bacteria from these phyla occur in diverse environments and are thought to mediate carbon and hydrogen cycles. Genomic analyses of a few representatives suggested that metabolic limitations have prevented their cultivation. Here we reconstructed 8 complete and 789 draft genomes from bacteria representing >35 phyla and documented features that consistently distinguish these organisms from other bacteria. We infer that this group, which may comprise >15% of the bacterial domain, has shared evolutionary history, and describe it as the candidate phyla radiation (CPR). All CPR genomes are small and most lack numerous biosynthetic pathways. Owing to divergent 16S ribosomal RNA (rRNA) gene sequences, 50-100% of organisms sampled from specific phyla would evade detection in typical cultivation-independent surveys. CPR organisms often have self-splicing introns and proteins encoded within their rRNA genes, a feature rarely reported in bacteria. Furthermore, they have unusual ribosome compositions. All are missing a ribosomal protein often absent in symbionts, and specific lineages are missing ribosomal proteins and biogenesis factors considered universal in bacteria. This implies different ribosome structures and biogenesis mechanisms, and underlines unusual biology across a large part of the bacterial domain.
McMaster University1, University of British Columbia2, Queen's University3, University of Toronto4, Peter MacCallum Cancer Centre5, Université de Sherbrooke6, Medical Research Council7, Ohio State University8, Université de Montréal9, Laval University10, Princess Margaret Cancer Centre11, Cross Cancer Institute12
TL;DR: This study randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes).
Abstract: BackgroundMost women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. MethodsWe randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. ResultsBetween March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was n...
National Institutes of Health1, Cornell University2, Memorial Sloan Kettering Cancer Center3, University of California, Los Angeles4, Rutgers University5, University of Wisconsin-Madison6, University of Rochester7, Ohio State University8, University of Washington9, Stanford University10, University of Texas MD Anderson Cancer Center11, Genentech12, Mayo Clinic13, Hofstra University14
TL;DR: The selective development of ibrutinib for the treatment of ABC DLBCL is supported, with the highest number of responses occurred in ABC tumors that lacked BCR mutations, suggesting that oncogenic BCR signaling in ABC does not require B CR mutations and might be initiated by non-genetic mechanisms.
Abstract: The two major subtypes of diffuse large B cell lymphoma (DLBCL)--activated B cell-like (ABC) and germinal center B cell-like (GCB)--arise by distinct mechanisms, with ABC selectively acquiring mutations that target the B cell receptor (BCR), fostering chronic active BCR signaling. The ABC subtype has a ∼40% cure rate with currently available therapies, which is worse than the rate for GCB DLBCL, and highlights the need for ABC subtype-specific treatment strategies. We hypothesized that ABC, but not GCB, DLBCL tumors would respond to ibrutinib, an inhibitor of BCR signaling. In a phase 1/2 clinical trial that involved 80 subjects with relapsed or refractory DLBCL, ibrutinib produced complete or partial responses in 37% (14/38) of those with ABC DLBCL, but in only 5% (1/20) of subjects with GCB DLBCL (P = 0.0106). ABC tumors with BCR mutations responded to ibrutinib frequently (5/9; 55.5%), especially those with concomitant myeloid differentiation primary response 88 (MYD88) mutations (4/5; 80%), a result that is consistent with in vitro cooperation between the BCR and MYD88 pathways. However, the highest number of responses occurred in ABC tumors that lacked BCR mutations (9/29; 31%), suggesting that oncogenic BCR signaling in ABC does not require BCR mutations and might be initiated by non-genetic mechanisms. These results support the selective development of ibrutinib for the treatment of ABC DLBCL.
École Polytechnique Fédérale de Lausanne1, Paris Diderot University2, University of California, Irvine3, Lawrence Berkeley National Laboratory4, Brookhaven National Laboratory5, Max Planck Society6, University of Portsmouth7, New Mexico State University8, University of Utah9, Harvard University10, University of Barcelona11, Aix-Marseille University12, University of Wyoming13, Pierre-and-Marie-Curie University14, Carnegie Mellon University15, Institut d'Astrophysique de Paris16, Drexel University17, Sejong University18, Pennsylvania State University19, Ohio State University20, University of Chicago21
TL;DR: In this paper, a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations was reported.
Abstract: We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations The study uses 137,562 quasars in the redshift range 2:1 z 3:5 from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III This sample contains three times the number of quasars used in previous studies The measured position of the BAO peak determines the angular distance, DA(z = 2:34) and expansion rate, H(z = 2:34), both on a scale set by the sound horizon at the drag epoch, rd We find DA=rd =
Fermilab1, Ohio State University2, University College London3, Autonomous University of Barcelona4, University of Pennsylvania5, Carnegie Learning6, University of Michigan7, Institut de Ciències de l'Espai8, Texas A&M University9, Lawrence Berkeley National Laboratory10, University of Chicago11, University of Illinois at Urbana–Champaign12, Australian Astronomical Observatory13, Argonne National Laboratory14, SLAC National Accelerator Laboratory15, Catalan Institution for Research and Advanced Studies16, Institute of Cosmology and Gravitation, University of Portsmouth17, California Institute of Technology18, Brookhaven National Laboratory19, Stanford University20
TL;DR: The Dark Energy Camera as mentioned in this paper was designed and constructed by the Dark Energy Survey Collaboration, and meets or exceeds the stringent requirements designed for the wide-field and supernova surveys for which the collaboration uses it.
Abstract: The Dark Energy Camera is a new imager with a 2.2-degree diameter field of view mounted at the prime focus of the Victor M. Blanco 4-meter telescope on Cerro Tololo near La Serena, Chile. The camera was designed and constructed by the Dark Energy Survey Collaboration, and meets or exceeds the stringent requirements designed for the wide-field and supernova surveys for which the collaboration uses it. The camera consists of a five element optical corrector, seven filters, a shutter with a 60 cm aperture, and a CCD focal plane of 250 micron thick fully-depleted CCDs cooled inside a vacuum Dewar. The 570 Mpixel focal plane comprises 62 2kx4k CCDs for imaging and 12 2kx2k CCDs for guiding and focus. The CCDs have 15 microns x15 microns pixels with a plate scale of 0.263 arc sec per pixel. A hexapod system provides state-of-the-art focus and alignment capability. The camera is read out in 20 seconds with 6-9 electrons readout noise. This paper provides a technical description of the camera's engineering, construction, installation, and current status.
TL;DR: In this paper, the authors proposed a strategy to minimize soil erosion, create positive organic carbon (SOC) and N budgets, enhance activity and species diversity of soil biota (micro, meso, and macro), and improve structural stability and pore geometry.
Abstract: Feeding the world population, 7.3 billion in 2015 and projected to increase to 9.5 billion by 2050, necessitates an increase in agricultural production of ~70% between 2005 and 2050. Soil degradation, characterized by decline in quality and decrease in ecosystem goods and services, is a major constraint to achieving the required increase in agricultural production. Soil is a non-renewable resource on human time scales with its vulnerability to degradation depending on complex interactions between processes, factors and causes occurring at a range of spatial and temporal scales. Among the major soil degradation processes are accelerated erosion, depletion of the soil organic carbon (SOC) pool and loss in biodiversity, loss of soil fertility and elemental imbalance, acidification and salinization. Soil degradation trends can be reversed by conversion to a restorative land use and adoption of recommended management practices. The strategy is to minimize soil erosion, create positive SOC and N budgets, enhance activity and species diversity of soil biota (micro, meso, and macro), and improve structural stability and pore geometry. Improving soil quality (i.e., increasing SOC pool, improving soil structure, enhancing soil fertility) can reduce risks of soil degradation (physical, chemical, biological and ecological) while improving the environment. Increasing the SOC pool to above the critical level (10 to 15 g/kg) is essential to set-in-motion the restorative trends. Site-specific techniques of restoring soil quality include conservation agriculture, integrated nutrient management, continuous vegetative cover such as residue mulch and cover cropping, and controlled grazing at appropriate stocking rates. The strategy is to produce “more from less” by reducing losses and increasing soil, water, and nutrient use efficiency.
TL;DR: This review suggests that development of N and P macronutrient nanofertilizers is a high research and development priority both for food production and environmental protection.
TL;DR: There are a large number of methods for quantifying porosity, and an increasingly complex idea of what it means to do so as discussed by the authors, which is why it is important to quantify the relationships between porosity and storage, transport and rock properties, however, the pore structure must be measured and quantitatively described.
Abstract: Porosity plays a clearly important role in geology. It controls fluid storage in aquifers, oil and gas fields and geothermal systems, and the extent and connectivity of the pore structure control fluid flow and transport through geological formations, as well as the relationship between the properties of individual minerals and the bulk properties of the rock. In order to quantify the relationships between porosity, storage, transport and rock properties, however, the pore structure must be measured and quantitatively described. The overall importance of porosity, at least with respect to the use of rocks as building stone was recognized by TS Hunt in his “Chemical and Geological Essays” (1875, reviewed by JD Dana 1875) who noted:
> “Other things being equal, it may properly be said that the value of a stone for building purposes is inversely as its porosity or absorbing power.”
In a Geological Survey report prepared for the U.S. Atomic Energy Commission, Manger (1963) summarized porosity and bulk density measurements for sedimentary rocks. He tabulated more than 900 items of porosity and bulk density data for sedimentary rocks with up to 2,109 porosity determinations per item. Amongst these he summarized several early studies, including those of Schwarz (1870–1871), Cook (1878), Wheeler (1896), Buckley (1898), Gary (1898), Moore (1904), Fuller (1906), Sorby (1908), Hirschwald (1912), Grubenmann et al. (1915), and Kessler (1919), many of which were concerned with rocks and clays of commercial utility. There have, of course, been many more such determinations since that time.
There are a large number of methods for quantifying porosity, and an increasingly complex idea of what it means to do so. Manger (1963) listed the techniques by which the porosity determinations he summarized were made. He separated these into seven methods for …
Emory University1, Harvard University2, University of Tennessee3, Wakayama Medical University4, University of British Columbia5, Mayo Clinic6, University of Verona7, Tokyo Medical University8, Ohio State University9, Tokyo Metropolitan Komagome Hospital10, Shinshu University11, Kanazawa University12, University of Ulsan13, Kyoto University14, Yokohama City University15, University of Greifswald16, Karolinska Institutet17, Kanazawa Medical University18, University of Toyama19, Kyushu University20, Nagoya City University21, Kansai Medical University22, Aix-Marseille University23, Tohoku University24, Sapporo Medical University25, Teikyo University26, University College London27, Peking Union Medical College28
TL;DR: A. H. Wallace, J. L. Carruthers, S. L€ ohr, Y. Khosroshahi, Z. Chari, E. Della-Torre, L. Frulloni, H.
Abstract: A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone
TL;DR: Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications.
Abstract: Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and differentiation, resulting in hamartomas of various organs, tumor formation, and altered neuronal migration. The phenotype is highly variable. Most individuals have seizures, commonly including infantile spasms, and there is variable intellectual disability and autism. Neonates can present with cardiac failure due to intracardiac rhabdomyomas. The likelihood of renal angiomyolipomas increases with age, and renal disease is the most common cause of death in adults with TSC. Pulmonary involvement occurs predominantly in women and carries a high morbidity and mortality. TSC is inherited as an autosomal dominant trait, but spontaneous mutations are common. A mutation of either TSC1 on chromosome 9 or TSC2 on chromosome 16 leads to dysfunction of hamartin or tuberin, respectively. These two proteins form a functional complex that modulates the mammalian target of rapamycin (mTOR) pathway. Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications. Consensus statements guide identification and optimal management of many of the TSC-related complications at diagnosis and throughout the lifespan. A multidisciplinary approach is necessary for optimal management of individuals with TSC.
TL;DR: Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 or M2 murine macrophages.
Abstract: Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages.
SUNY Downstate Medical Center1, State University of New York System2, University of Copenhagen3, Albert Einstein College of Medicine4, Duke University5, Johns Hopkins Bayview Medical Center6, University of California, San Francisco7, University of Alabama at Birmingham8, Creighton University9, Ohio State University10, Kuwait University11, Springfield College12
TL;DR: 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1 are presented and represent the best-documented, least controversial results.
Boston Children's Hospital1, NewYork–Presbyterian Hospital2, University of Chicago3, University of Chile4, Ohio State University5, University of Barcelona6, University of Adelaide7, Georgetown University8, Baylor College of Medicine9, American University of Beirut10, University of Pittsburgh11, Sanjay Gandhi Post Graduate Institute of Medical Sciences12
TL;DR: While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.
Abstract: Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological feat
TL;DR: The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV.
Abstract: The gamma-ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky emission component commonly called the isotropic diffuse gamma-ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission, and a longer data accumulation of 50 months, allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature, and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 plus or minus 0.02 and a break energy of (279 plus or minus 52) GeV using our baseline diffuse Galactic emission model. The total intensity attributed to the IGRB is (7.2 plus or minus 0.6) x 10(exp -6) cm(exp -2) s(exp -1) sr(exp -1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.