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Showing papers by "Ohio State University published in 2014"


Journal ArticleDOI
Keith A. Olive1, Kaustubh Agashe2, Claude Amsler3, Mario Antonelli  +222 moreInstitutions (107)
TL;DR: The review as discussed by the authors summarizes much of particle physics and cosmology using data from previous editions, plus 3,283 new measurements from 899 Japers, including the recently discovered Higgs boson, leptons, quarks, mesons and baryons.
Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

7,337 citations


Journal ArticleDOI
TL;DR: A tutorial is provided illustrating an approach to estimation of and inference about direct, indirect, and total effects in statistical mediation analysis with a multicategorical independent variable that reproduces the observed and adjusted group means while also generating effects having simple interpretations.
Abstract: Virtually all discussions and applications of statistical mediation analysis have been based on the condition that the independent variable is dichotomous or continuous, even though investigators frequently are interested in testing mediation hypotheses involving a multicategorical independent variable (such as two or more experimental conditions relative to a control group). We provide a tutorial illustrating an approach to estimation of and inference about direct, indirect, and total effects in statistical mediation analysis with a multicategorical independent variable. The approach is mathematically equivalent to analysis of (co)variance and reproduces the observed and adjusted group means while also generating effects having simple interpretations. Supplementary material available online includes extensions to this approach and Mplus, SPSS, and SAS code that implements it.

2,318 citations


Journal ArticleDOI
John N. Weinstein1, Rehan Akbani1, Bradley M. Broom1, Wenyi Wang1  +293 moreInstitutions (30)
01 Jan 2014-Nature
TL;DR: Ch Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Abstract: Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. To date, no molecularly targeted agents have been approved for the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#termsThis paper is distributed under the terms of the Creative Commons. Attribution-Non-Commercial-Share Alike license, and the online version of the paper is freely available to all readers.

2,257 citations


Journal ArticleDOI
TL;DR: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma, and progression-free survival was prolonged but did not reach the prespecified improvement target.
Abstract: Background Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. Methods In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary ...

2,181 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.
Abstract: MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in cellular processes such as inflammation, cell-cycle regulation, stress response, differentiation, apoptosis, and migration. Thus, miRNAs have been implicated in the regulation of virtually all signaling circuits within a cell, and their dysregulation has been shown to play an essential role in the development and progression of cancer. Here, after a brief description of miRNA genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies.

1,899 citations


Journal ArticleDOI
TL;DR: In this article, the authors present a survey of self-interference mitigation techniques for in-band full-duplex (IBFD) wireless systems and discuss the challenges and opportunities in the design and analysis of IBFD wireless systems.
Abstract: In-band full-duplex (IBFD) operation has emerged as an attractive solution for increasing the throughput of wireless communication systems and networks. With IBFD, a wireless terminal is allowed to transmit and receive simultaneously in the same frequency band. This tutorial paper reviews the main concepts of IBFD wireless. One of the biggest practical impediments to IBFD operation is the presence of self-interference, i.e., the interference that the modem's transmitter causes to its own receiver. This tutorial surveys a wide range of IBFD self-interference mitigation techniques. Also discussed are numerous other research challenges and opportunities in the design and analysis of IBFD wireless systems.

1,752 citations


Journal ArticleDOI
TL;DR: The potential applications of microRNAs for the clinical assessment of patient outcome in cancer, as well as in cancer monitoring and therapy are reviewed.

1,680 citations


Journal ArticleDOI
TL;DR: A “state of the science” review of current research into causes and risk factors for gliomas in adults is provided.
Abstract: Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors Although relatively rare, they cause significant mortality and morbidity Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5% A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome Genomic analyses of glioma have also produced new evidence about risk and prognosis Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma Many risk factors have been examined as potential contributors to glioma risk Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s) The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults

1,536 citations


Journal ArticleDOI
TL;DR: In this article, the authors reported that NGC 2617 went through a dramatic outburst, during which its X-ray flux increased by over an order of magnitude followed by an increase of its optical/ultraviolet (UV) continuum flux.
Abstract: After the All-Sky Automated Survey for SuperNovae discovered a significant brightening of the inner region of NGC 2617, we began a ∼70 day photometric and spectroscopic monitoring campaign from the X-ray through near-infrared (NIR) wavelengths. We report that NGC 2617 went through a dramatic outburst, during which its X-ray flux increased by over an order of magnitude followed by an increase of its optical/ultraviolet (UV) continuum flux by almost an order of magnitude. NGC 2617, classified as a Seyfert 1.8 galaxy in 2003, is now a Seyfert 1 due to the appearance of broad optical emission lines and a continuum blue bump. Such 'changing look active galactic nuclei (AGNs)' are rare and provide us with important insights about AGN physics. Based on the Hβ line width and the radius-luminosity relation, we estimate the mass of central black hole (BH) to be (4 ± 1) × 10{sup 7} M {sub ☉}. When we cross-correlate the light curves, we find that the disk emission lags the X-rays, with the lag becoming longer as we move from the UV (2-3 days) to the NIR (6-9 days). Also, the NIR is more heavily temporally smoothed than the UV. This can largely be explained bymore » a simple model of a thermally emitting thin disk around a BH of the estimated mass that is illuminated by the observed, variable X-ray fluxes.« less

1,473 citations


Journal ArticleDOI
TL;DR: In this paper, the dominant electronic and chemical mechanisms that influence the performance of metal-oxide-based resistive-type gas sensors are discussed, including p-n and n-n potential barrier manipulation, n-p-n response type inversions, spillover effects, synergistic catalytic behavior, and microstructure enhancement.
Abstract: Metal oxide-based resistive-type gas sensors are solid-state devices which are widely used in a number of applications from health and safety to energy efficiency and emission control. Nanomaterials such as nanowires, nanorods, and nanoparticles have dominated the research focus in this field due to their large number of surface sites facilitating surface reactions. Previous studies have shown that incorporating two or more metal oxides to form a heterojunction interface can have drastic effects on gas sensor performance, especially the selectivity. Recently, these effects have been amplified by designing heterojunctions on the nano-scale. These designs have evolved from mixed commercial powders and bi-layer films to finely-tuned core–shell and hierarchical brush-like nanocomposites. This review details the various morphological classes currently available for nanostructured metal-oxide based heterojunctions and then presents the dominant electronic and chemical mechanisms that influence the performance of these materials as resistive-type gas sensors. Mechanisms explored include p–n and n–n potential barrier manipulation, n–p–n response type inversions, spill-over effects, synergistic catalytic behavior, and microstructure enhancement. Tables are presented summarizing these works specifically for SnO2, ZnO, TiO2, In2O3, Fe2O3, MoO3, Co3O4, and CdO-based nanocomposites. Recent developments are highlighted and likely future trends are explored.

1,392 citations


Journal ArticleDOI
TL;DR: Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL.
Abstract: Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progressionfree survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)

Journal ArticleDOI
TL;DR: In this paper, the authors provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive quantitative structure-activity relationship models.
Abstract: Quantitative structure–activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR stu...

Journal ArticleDOI
TL;DR: Analysis of published data reveals evidence for stray gas contamination, surface water impacts in areas of intensive shale gas development, and the accumulation of radium isotopes in some disposal and spill sites.
Abstract: The rapid rise of shale gas development through horizontal drilling and high volume hydraulic fracturing has expanded the extraction of hydrocarbon resources in the U.S. The rise of shale gas development has triggered an intense public debate regarding the potential environmental and human health effects from hydraulic fracturing. This paper provides a critical review of the potential risks that shale gas operations pose to water resources, with an emphasis on case studies mostly from the U.S. Four potential risks for water resources are identified: (1) the contamination of shallow aquifers with fugitive hydrocarbon gases (i.e., stray gas contamination), which can also potentially lead to the salinization of shallow groundwater through leaking natural gas wells and subsurface flow; (2) the contamination of surface water and shallow groundwater from spills, leaks, and/or the disposal of inadequately treated shale gas wastewater; (3) the accumulation of toxic and radioactive elements in soil or stream sediments near disposal or spill sites; and (4) the overextraction of water resources for high-volume hydraulic fracturing that could induce water shortages or conflicts with other water users, particularly in water-scarce areas. Analysis of published data (through January 2014) reveals evidence for stray gas contamination, surface water impacts in areas of intensive shale gas development, and the accumulation of radium isotopes in some disposal and spill sites. The direct contamination of shallow groundwater from hydraulic fracturing fluids and deep formation waters by hydraulic fracturing itself, however, remains controversial.

Journal ArticleDOI
TL;DR: The 10th public data release (DR10) from the Sloan Digital Sky Survey (SDSS-III) was released in 2013 as mentioned in this paper, which includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopy data from Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July.
Abstract: The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the Tenth Public Data Release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ~ 22,500 300 fiber spectrograph covering 1.514-1.696 μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the Milky Way. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the Ninth Data Release. DR10 includes a total of 1,507,954 BOSS spectra comprising 927,844 galaxy spectra, 182,009 quasar spectra, and 159,327 stellar spectra selected over 6373.2 deg2.

Journal ArticleDOI
M. G. Aartsen1, Markus Ackermann, Jenni Adams2, Juanan Aguilar3  +299 moreInstitutions (41)
TL;DR: Results from an analysis with a third year of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ.
Abstract: A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

Journal ArticleDOI
TL;DR: The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007.
Abstract: The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

Journal ArticleDOI
Kathryn G. Roberts1, Yongjin Li, Debbie Payne-Turner1, Richard C. Harvey1, Yung-Li Yang1, Dehua Pei, Kelly McCastlain1, Li Ding2, Li Ding3, Changxue Lu3, Changxue Lu2, Guangchun Song1, Jing Ma1, Jared Becksfort, Michael Rusch, S. C. Chen1, John Easton, J. Cheng, Kristy Boggs, Natalia Santiago-Morales1, Ilaria Iacobucci1, Robert S. Fulton2, Robert S. Fulton3, Ji Wen1, Marcus B. Valentine, Cheng Cheng, Steven W. Paugh, Meenakshi Devidas4, Meenakshi Devidas5, I-Ming Chen4, S. Reshmi4, S. Reshmi6, Amy Smith6, Erin Hedlund, Pankaj Gupta, Panduka Nagahawatte, Gang Wu, Xiang Chen, Donald Yergeau, Bhavin Vadodaria, Heather L. Mulder, Naomi J. Winick7, Eric Larsen, William L. Carroll4, William L. Carroll8, Nyla A. Heerema, Andrew J. Carroll9, G. Grayson10, Sarah K. Tasian11, Andrew S. Moore12, F. Keller13, Melissa Frei-Jones14, J. A. Whitlock15, Elizabeth A. Raetz, Deborah L. White, Timothy P. Hughes16, J. M. Guidry Auvil4, Malcolm A. Smith17, Malcolm A. Smith4, Guido Marcucci7, Clara D. Bloomfield7, Krzysztof Mrózek7, Jessica Kohlschmidt7, Jessica Kohlschmidt17, Wendy Stock18, Steven M. Kornblau19, Marina Konopleva20, Elisabeth Paietta21, Ching-Hon Pui, Sima Jeha, Mary V. Relling4, William E. Evans, Daniela S. Gerhard4, Julie M. Gastier-Foster6, Julie M. Gastier-Foster4, Elaine R. Mardis, Richard K. Wilson, Mignon L. Loh22, Mignon L. Loh4, James R. Downing4, James R. Downing1, Stephen P. Hunger23, Stephen P. Hunger4, Cheryl L. Willman1, Cheryl L. Willman4, Jinghui Zhang4, Charles G. Mullighan4, Charles G. Mullighan1 
TL;DR: Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors.
Abstract: BACKGROUND Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. METHODS We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL. RESULTS Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6–NTRK3 fusion was sensitive to crizotinib. CONCLUSIONS Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and others.)

Journal ArticleDOI
05 Feb 2014-JAMA
TL;DR: Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia and the clinical implications of this association warrant further investigation.
Abstract: Importance Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. Objective To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. Design, Setting, and Participants Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. Main Outcomes and Measures Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 ( Results Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P Conclusions and Relevance Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.

Journal ArticleDOI
TL;DR: Results in various test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK, outperform the other targets in terms of objective intelligibility and quality metrics, and that masking based targets, in general, are significantly better than spectral envelope based targets.
Abstract: Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the use of binary targets. In this study, we evaluate and compare separation results by using different training targets, including the IBM, the target binary mask, the ideal ratio mask (IRM), the short-time Fourier transform spectral magnitude and its corresponding mask (FFT-MASK), and the Gammatone frequency power spectrum. Our results in various test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK, outperform the other targets in terms of objective intelligibility and quality metrics. In addition, we find that masking based targets, in general, are significantly better than spectral envelope based targets. We also present comparisons with recent methods in non-negative matrix factorization and speech enhancement, which show clear performance advantages of supervised speech separation.

Journal ArticleDOI
TL;DR: Functional analysis showed that the C481S mutation of BTK results in a protein that is only reversibly inhibited by ibrutinib, which underscores the importance of the B-cell-receptor pathway in the mechanism of action of ibrUTinib in CLL.
Abstract: Background Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. Methods We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. In addition, we performed Ion Torrent sequencing for identified resistance mutations on samples from nine patients with prolonged lymphocytosis. Results We identified a cysteine-to-serine mutation in BTK at the binding site of ibrutinib in five patients and identified three distinct mutati...

Journal ArticleDOI
TL;DR: In this article, the authors outline a set of CSA actions needed from public, private and civil society stakeholders: building evidence; increasing local institutional effectiveness; fostering coherence between climate and agricultural policies; and linking climate and agriculture financing.
Abstract: Climate-smart agriculture (CSA) is an approach to the development of agricultural systems intended to help support food security under climate change. This Perspective outlines a set of CSA actions needed from public, private and civil society stakeholders: building evidence; increasing local institutional effectiveness; fostering coherence between climate and agricultural policies; and linking climate and agricultural financing.

Journal ArticleDOI
TL;DR: Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptylines HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPn treatment options.
Abstract: Purpose To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. Methods A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. Results A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the ba...

Journal ArticleDOI
TL;DR: In this single-group, open-label, phase 2 study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment.
Abstract: Background Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin’s lymphomas. Methods In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin’s lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety. Results The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin’s lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenstrom’s macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin’s lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%). Conclusions In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin’s lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424.)

Journal ArticleDOI
TL;DR: The authors compared variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants and found that the results of these experiments are more dependent on the effect itself than on the sample and setting used to investigate the effect.
Abstract: Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect.


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TL;DR: The ALICE experiment at the CERN Large Hadron Collider as mentioned in this paper continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams.
Abstract: ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.

Journal ArticleDOI
Sofia Khan1, Dario Greco2, Dario Greco1, Kyriaki Michailidou3  +158 moreInstitutions (54)
12 Nov 2014-PLOS ONE
TL;DR: Five miRNA binding site SNPs associated significantly with breast cancer risk are located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively, which belongs to miRNA machinery genes and has a central role in initial miRNA processing.
Abstract: Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Journal ArticleDOI
TL;DR: The initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative effects of retinal detachment, and lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases, such as age-related macular degeneration, for which intervention should ideally be applied before the onset ofretinal thinning.

Proceedings ArticleDOI
14 Sep 2014
TL;DR: The experimental results demonstrate that the proposed approach effectively learns emotional information from low-level features and leads to 20% relative accuracy improvement compared to the state of the art approaches.
Abstract: Speech emotion recognition is a challenging problem partly because it is unclear what features are effective for the task. In this paper we propose to utilize deep neural networks (DNNs) to extract high level features from raw data and show that they are effective for speech emotion recognition. We first produce an emotion state probability distribution for each speech segment using DNNs. We then construct utterance-level features from segment-level probability distributions. These utterancelevel features are then fed into an extreme learning machine (ELM), a special simple and efficient single-hidden-layer neural network, to identify utterance-level emotions. The experimental results demonstrate that the proposed approach effectively learns emotional information from low-level features and leads to 20% relative accuracy improvement compared to the stateof-the-art approaches.

Journal ArticleDOI
TL;DR: The data suggest the breast-cancer risk for PALB2 mutation carriers may overlap with that for BRCA1 mutation carriers, and loss-of-function mutations in PALB1 are an important cause of hereditary breast cancer.
Abstract: The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P < 0.001) and by other familial factors (P = 0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age. CONCLUSIONS Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them. Our data suggest the breast-cancer risk for PALB2 mutation carriers may overlap with that for BRCA2 mutation carriers. (Funded by the European Research Council and others.) abstr act