scispace - formally typeset
Search or ask a question

Showing papers by "Pierre-and-Marie-Curie University published in 2017"


Journal ArticleDOI
TL;DR: Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenIB treatment, and future trials should explore combinations of regorAFenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafanib and regorafinib.

2,543 citations


Journal ArticleDOI
Shadab Alam1, Metin Ata2, Stephen Bailey3, Florian Beutler3, Dmitry Bizyaev4, Dmitry Bizyaev5, Jonathan Blazek6, Adam S. Bolton7, Joel R. Brownstein7, Angela Burden8, Chia-Hsun Chuang2, Chia-Hsun Chuang9, Johan Comparat9, Antonio J. Cuesta10, Kyle S. Dawson7, Daniel J. Eisenstein11, Stephanie Escoffier12, Héctor Gil-Marín13, Héctor Gil-Marín14, Jan Niklas Grieb15, Nick Hand16, Shirley Ho1, Karen Kinemuchi4, D. Kirkby17, Francisco S. Kitaura2, Francisco S. Kitaura16, Francisco S. Kitaura3, Elena Malanushenko4, Viktor Malanushenko4, Claudia Maraston18, Cameron K. McBride11, Robert C. Nichol18, Matthew D. Olmstead19, Daniel Oravetz4, Nikhil Padmanabhan8, Nathalie Palanque-Delabrouille, Kaike Pan4, Marcos Pellejero-Ibanez20, Marcos Pellejero-Ibanez21, Will J. Percival18, Patrick Petitjean22, Francisco Prada9, Francisco Prada21, Adrian M. Price-Whelan23, Beth Reid16, Beth Reid3, Sergio Rodríguez-Torres9, Sergio Rodríguez-Torres21, Natalie A. Roe3, Ashley J. Ross18, Ashley J. Ross6, Nicholas P. Ross24, Graziano Rossi25, Jose Alberto Rubino-Martin20, Jose Alberto Rubino-Martin21, Shun Saito15, Salvador Salazar-Albornoz15, Lado Samushia26, Ariel G. Sánchez15, Siddharth Satpathy1, David J. Schlegel3, Donald P. Schneider27, Claudia G. Scóccola9, Claudia G. Scóccola28, Claudia G. Scóccola29, Hee-Jong Seo30, Erin Sheldon31, Audrey Simmons4, Anže Slosar31, Michael A. Strauss23, Molly E. C. Swanson11, Daniel Thomas18, Jeremy L. Tinker32, Rita Tojeiro33, Mariana Vargas Magaña1, Mariana Vargas Magaña34, Jose Alberto Vazquez31, Licia Verde, David A. Wake35, David A. Wake36, Yuting Wang18, Yuting Wang37, David H. Weinberg6, Martin White16, Martin White3, W. Michael Wood-Vasey38, Christophe Yèche, Idit Zehavi39, Zhongxu Zhai33, Gong-Bo Zhao18, Gong-Bo Zhao37 
TL;DR: In this article, the authors present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III.
Abstract: We present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. Our combined galaxy sample comprises 1.2 million massive galaxies over an effective area of 9329 deg^2 and volume of 18.7 Gpc^3, divided into three partially overlapping redshift slices centred at effective redshifts 0.38, 0.51 and 0.61. We measure the angular diameter distance and Hubble parameter H from the baryon acoustic oscillation (BAO) method, in combination with a cosmic microwave background prior on the sound horizon scale, after applying reconstruction to reduce non-linear effects on the BAO feature. Using the anisotropic clustering of the pre-reconstruction density field, we measure the product D_MH from the Alcock–Paczynski (AP) effect and the growth of structure, quantified by fσ_8(z), from redshift-space distortions (RSD). We combine individual measurements presented in seven companion papers into a set of consensus values and likelihoods, obtaining constraints that are tighter and more robust than those from any one method; in particular, the AP measurement from sub-BAO scales sharpens constraints from post-reconstruction BAOs by breaking degeneracy between D_M and H. Combined with Planck 2016 cosmic microwave background measurements, our distance scale measurements simultaneously imply curvature Ω_K = 0.0003 ± 0.0026 and a dark energy equation-of-state parameter w = −1.01 ± 0.06, in strong affirmation of the spatially flat cold dark matter (CDM) model with a cosmological constant (ΛCDM). Our RSD measurements of fσ_8, at 6 per cent precision, are similarly consistent with this model. When combined with supernova Ia data, we find H_0 = 67.3 ± 1.0 km s^−1 Mpc^−1 even for our most general dark energy model, in tension with some direct measurements. Adding extra relativistic species as a degree of freedom loosens the constraint only slightly, to H_0 = 67.8 ± 1.2 km s^−1 Mpc^−1. Assuming flat ΛCDM, we find Ω_m = 0.310 ± 0.005 and H_0 = 67.6 ± 0.5 km s^−1 Mpc^−1, and we find a 95 per cent upper limit of 0.16 eV c^−2 on the neutrino mass sum.

2,413 citations


Journal ArticleDOI
12 Dec 2017-JAMA
TL;DR: In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints.
Abstract: Importance Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Objective Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin–stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists’ diagnoses in a diagnostic setting. Design, Setting, and Participants Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Exposures Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. Main Outcomes and Measures The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. Results The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% [95% CI, 64.3%-80.4%]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95% CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884];P Conclusions and Relevance In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting.

2,116 citations


Journal ArticleDOI
TL;DR: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice and the stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment.

1,910 citations


Journal ArticleDOI
TL;DR: The current summary of the EAU Muscle- invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer.

1,209 citations


Journal ArticleDOI
TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.

1,200 citations


Journal ArticleDOI
Steven R. Majewski1, Ricardo P. Schiavon2, Peter M. Frinchaboy3, Carlos Allende Prieto4, Carlos Allende Prieto5, Robert H. Barkhouser6, Dmitry Bizyaev7, Dmitry Bizyaev8, Basil Blank, Sophia Brunner1, Adam Burton1, Ricardo Carrera4, Ricardo Carrera5, S. Drew Chojnowski1, S. Drew Chojnowski7, Katia Cunha9, Courtney R. Epstein10, Greg Fitzgerald, Ana E. García Pérez1, Ana E. García Pérez4, Fred Hearty11, Fred Hearty1, Chuck Henderson, Jon A. Holtzman7, Jennifer A. Johnson10, Charles R. Lam1, James E. Lawler12, Paul Maseman9, Szabolcs Mészáros5, Szabolcs Mészáros13, Szabolcs Mészáros4, Matthew J. Nelson1, Duy Coung Nguyen14, David L. Nidever1, David L. Nidever15, Marc H. Pinsonneault10, Matthew Shetrone16, Stephen A. Smee6, Verne V. Smith9, T. Stolberg, Michael F. Skrutskie1, E. Walker1, John C. Wilson1, Gail Zasowski6, Gail Zasowski1, Friedrich Anders17, Sarbani Basu18, Stephane Beland19, Michael R. Blanton20, Jo Bovy14, Jo Bovy21, Joel R. Brownstein22, Joleen K. Carlberg1, Joleen K. Carlberg23, William J. Chaplin24, William J. Chaplin25, Cristina Chiappini17, Daniel J. Eisenstein26, Yvonne Elsworth25, Diane Feuillet7, Scott W. Fleming27, Scott W. Fleming28, Jessica Galbraith-Frew22, Rafael A. García29, D. Anibal García-Hernández5, D. Anibal García-Hernández4, Bruce Gillespie6, Léo Girardi30, James E. Gunn21, Sten Hasselquist1, Sten Hasselquist7, Michael R. Hayden7, Saskia Hekker31, Saskia Hekker24, Inese I. Ivans22, Karen Kinemuchi7, Mark A. Klaene7, Suvrath Mahadevan11, Savita Mathur32, Benoit Mosser33, Demitri Muna10, Jeffrey A. Munn, Robert C. Nichol, Robert W. O'Connell1, John K. Parejko18, Annie C. Robin34, H. J. Rocha-Pinto35, M. Schultheis36, Aldo Serenelli4, Neville Shane1, Victor Silva Aguirre24, Jennifer Sobeck1, Benjamin A. Thompson3, Nicholas W. Troup1, David H. Weinberg10, Olga Zamora5, Olga Zamora4 
TL;DR: In this article, the Hungarian National Research, Development and Innovation Office (K-119517) and Hungarian National Science Foundation (KNFI) have proposed a method to detect the presence of asteroids in Earth's magnetic field.
Abstract: National Science Foundation [AST-1109178, AST-1616636]; Gemini Observatory; Spanish Ministry of Economy and Competitiveness [AYA-2011-27754]; NASA [NNX12AE17G]; Hungarian Academy of Sciences; Hungarian NKFI of the Hungarian National Research, Development and Innovation Office [K-119517]; Alfred P. Sloan Foundation; National Science Foundation; U.S. Department of Energy Office of Science

1,193 citations


Journal ArticleDOI
TL;DR: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR, addressing the relative merits of using oral H1‐antihistamines, intranasal H1-antihistsamines, IntranasAL corticosteroids, and leukotriene receptor antagonists either alone or in combination.
Abstract: Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

1,098 citations


Journal ArticleDOI
TL;DR: The 2017 roadmap of terahertz frequency electromagnetic radiation (100 GHz-30 THz) as discussed by the authors provides a snapshot of the present state of THz science and technology in 2017, and provides an opinion on the challenges and opportunities that the future holds.
Abstract: Science and technologies based on terahertz frequency electromagnetic radiation (100 GHz–30 THz) have developed rapidly over the last 30 years. For most of the 20th Century, terahertz radiation, then referred to as sub-millimeter wave or far-infrared radiation, was mainly utilized by astronomers and some spectroscopists. Following the development of laser based terahertz time-domain spectroscopy in the 1980s and 1990s the field of THz science and technology expanded rapidly, to the extent that it now touches many areas from fundamental science to 'real world' applications. For example THz radiation is being used to optimize materials for new solar cells, and may also be a key technology for the next generation of airport security scanners. While the field was emerging it was possible to keep track of all new developments, however now the field has grown so much that it is increasingly difficult to follow the diverse range of new discoveries and applications that are appearing. At this point in time, when the field of THz science and technology is moving from an emerging to a more established and interdisciplinary field, it is apt to present a roadmap to help identify the breadth and future directions of the field. The aim of this roadmap is to present a snapshot of the present state of THz science and technology in 2017, and provide an opinion on the challenges and opportunities that the future holds. To be able to achieve this aim, we have invited a group of international experts to write 18 sections that cover most of the key areas of THz science and technology. We hope that The 2017 Roadmap on THz science and technology will prove to be a useful resource by providing a wide ranging introduction to the capabilities of THz radiation for those outside or just entering the field as well as providing perspective and breadth for those who are well established. We also feel that this review should serve as a useful guide for government and funding agencies.

1,068 citations


Journal ArticleDOI
Elena Aprile1, Jelle Aalbers2, F. Agostini, M. Alfonsi3, F. D. Amaro4, M. Anthony1, F. Arneodo5, P. Barrow6, Laura Baudis6, Boris Bauermeister7, M. L. Benabderrahmane5, T. Berger8, P. A. Breur2, April S. Brown2, Ethan Brown8, S. Bruenner9, Giacomo Bruno, Ran Budnik10, L. Bütikofer11, J. Calvén7, João Cardoso4, M. Cervantes12, D. Cichon9, D. Coderre11, Auke-Pieter Colijn2, Jan Conrad7, Jean-Pierre Cussonneau13, M. P. Decowski2, P. de Perio1, P. Di Gangi14, A. Di Giovanni5, Sara Diglio13, G. Eurin9, J. Fei15, A. D. Ferella7, A. Fieguth16, W. Fulgione, A. Gallo Rosso, Michelle Galloway6, F. Gao1, M. Garbini14, Robert Gardner17, C. Geis3, Luke Goetzke1, L. Grandi17, Z. Greene1, C. Grignon3, C. Hasterok9, E. Hogenbirk2, J. Howlett1, R. Itay10, B. Kaminsky11, Shingo Kazama6, G. Kessler6, A. Kish6, H. Landsman10, R. F. Lang12, D. Lellouch10, L. Levinson10, Qing Lin1, Sebastian Lindemann9, Manfred Lindner9, F. Lombardi15, J. A. M. Lopes4, A. Manfredini10, I. Mariș5, T. Marrodán Undagoitia9, Julien Masbou13, F. V. Massoli14, D. Masson12, D. Mayani6, M. Messina1, K. Micheneau13, A. Molinario, K. Morâ7, M. Murra16, J. Naganoma18, Kaixuan Ni15, Uwe Oberlack3, P. Pakarha6, Bart Pelssers7, R. Persiani13, F. Piastra6, J. Pienaar12, V. Pizzella9, M.-C. Piro8, Guillaume Plante1, N. Priel10, L. Rauch9, S. Reichard6, C. Reuter12, B. Riedel17, A. Rizzo1, S. Rosendahl16, N. Rupp9, R. Saldanha17, J.M.F. dos Santos4, Gabriella Sartorelli14, M. Scheibelhut3, S. Schindler3, J. Schreiner9, Marc Schumann11, L. Scotto Lavina19, M. Selvi14, P. Shagin18, E. Shockley17, Manuel Gameiro da Silva4, H. Simgen9, M. V. Sivers11, A. Stein20, S. Thapa17, Dominique Thers13, A. Tiseni2, Gian Carlo Trinchero, C. Tunnell17, M. Vargas16, N. Upole17, Hui Wang20, Zirui Wang, Yuehuan Wei6, Ch. Weinheimer16, J. Wulf6, J. Ye15, Yanxi Zhang1, T. Zhu1 
TL;DR: The first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy, are reported and a profile likelihood analysis shows that the data are consistent with the background-only hypothesis.
Abstract: We report the first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of this kind The blinded search used 342 live days of data acquired between November 2016 and January 2017 Inside the (1042±12)-kg fiducial mass and in the [5,40] keVnr energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (193±025)×10-4 events/(kg×day×keVee), the lowest ever achieved in such a dark matter detector A profile likelihood analysis shows that the data are consistent with the background-only hypothesis We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c2, with a minimum of 77×10-47 cm2 for 35-GeV/c2 WIMPs at 90% CL

1,061 citations


Journal ArticleDOI
TL;DR: This work highlights this rapidly advancing area of algal science with a particular focus on the key research required to assess better the health benefits of an alga or algal product.
Abstract: Global demand for macroalgal and microalgal foods is growing, and algae are increasingly being consumed for functional benefits beyond the traditional considerations of nutrition and health. There is substantial evidence for the health benefits of algal-derived food products, but there remain considerable challenges in quantifying these benefits, as well as possible adverse effects. First, there is a limited understanding of nutritional composition across algal species, geographical regions, and seasons, all of which can substantially affect their dietary value. The second issue is quantifying which fractions of algal foods are bioavailable to humans, and which factors influence how food constituents are released, ranging from food preparation through genetic differentiation in the gut microbiome. Third is understanding how algal nutritional and functional constituents interact in human metabolism. Superimposed considerations are the effects of harvesting, storage, and food processing techniques that can dramatically influence the potential nutritive value of algal-derived foods. We highlight this rapidly advancing area of algal science with a particular focus on the key research required to assess better the health benefits of an alga or algal product. There are rich opportunities for phycologists in this emerging field, requiring exciting new experimental and collaborative approaches.

Journal ArticleDOI
TL;DR: The notion of three-dimensional topological insulators is extended to systems that host no gapless surface states but exhibit topologically protected gapless hinge states and it is shown that SnTe as well as surface-modified Bi2TeI, BiSe, and BiTe are helical higher-order topology insulators.
Abstract: Three-dimensional topological (crystalline) insulators are materials with an insulating bulk, but conducting surface states which are topologically protected by time-reversal (or spatial) symmetries. Here, we extend the notion of three-dimensional topological insulators to systems that host no gapless surface states, but exhibit topologically protected gapless hinge states. Their topological character is protected by spatio-temporal symmetries, of which we present two cases: (1) Chiral higher-order topological insulators protected by the combination of time-reversal and a four-fold rotation symmetry. Their hinge states are chiral modes and the bulk topology is $\mathbb{Z}_2$-classified. (2) Helical higher-order topological insulators protected by time-reversal and mirror symmetries. Their hinge states come in Kramers pairs and the bulk topology is $\mathbb{Z}$-classified. We provide the topological invariants for both cases. Furthermore we show that SnTe as well as surface-modified Bi$_2$TeI, BiSe, and BiTe are helical higher-order topological insulators and propose a realistic experimental setup to detect the hinge states.

Journal ArticleDOI
Rebecca Sims1, Sven J. van der Lee2, Adam C. Naj3, Céline Bellenguez4  +484 moreInstitutions (120)
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Journal ArticleDOI
13 Jan 2017-Gut
TL;DR: This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
Abstract: Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.

Journal ArticleDOI
TL;DR: The novel European Thyroid Imaging and Reporting Data System, called EU-TIRADS, aims to serve physicians in their clinical practice, to enhance the interobserver reproducibility of descriptions, and to simplify communication of the results.
Abstract: Thyroid ultrasound (US) is a key examination for the management of thyroid nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is a mandatory step in the workup of thyroid nodules. The main disadvantage of the method is that it is operator dependent. Thyroid US assessment of the risk of malignancy is crucial in patients with nodules, in order to select those who should have a fine needle aspiration (FNA) biopsy performed. Due to the pivotal role of thyroid US in the management of patients with nodules, the European Thyroid Association convened a panel of international experts to set up European guidelines on US risk stratification of thyroid nodules. Based on a review of the literature and on the American Association of Clinical Endocrinologists, American Thyroid Association, and Korean guidelines, the panel created the novel European Thyroid Imaging and Reporting Data System, called EU-TIRADS. This comprises a thyroid US lexicon; a standardized report; definitions of benign and low-, intermediate-, and high-risk nodules, with the estimated risks of malignancy in each category; and indications for FNA. Illustrated by numerous US images, the EU-TIRADS aims to serve physicians in their clinical practice, to enhance the interobserver reproducibility of descriptions, and to simplify communication of the results.

Journal ArticleDOI
TL;DR: In elderly patients with glioblastoma, the addition of temozolomide to short‐course radiotherapy resulted in longer survival than short‐ Course radiotherapy alone.
Abstract: BackgroundGlioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown. MethodsWe conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma. Patients were randomly assigned to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide. ResultsA total of 562 patients underwent randomization, 281 to each group. The median age was 73 years (range, 65 to 90). The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone (9.3 months vs. 7.6 months; hazard ratio for death, 0.67; 95% confidence interval [CI], 0.56 to 0.80; P<0.0...

Book ChapterDOI
TL;DR: The many discoveries that led to the study of lncRNAs are discussed, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s, to focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts.
Abstract: The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed “non-coding.” It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.


Journal ArticleDOI
Roel Aaij1, Bernardo Adeva2, Marco Adinolfi3, Ziad Ajaltouni4  +818 moreInstitutions (68)
TL;DR: In this article, a test of lepton universality is performed by measuring the ratio of the branching fractions of the B$0$ → K$*0}$ e$+}$ π$−}$ decays, and the ratio is measured in two regions of the dilepton invariant mass squared.
Abstract: A test of lepton universality, performed by measuring the ratio of the branching fractions of the B$^{0}$ → K$^{*0}$ μ$^{+}$ μ$^{−}$ and B$^{0}$ → K$^{*0}$ e$^{+}$ e$^{−}$ decays, $ {R}_{K^{*0}} $ , is presented. The K$^{*0}$ meson is reconstructed in the final state K$^{+}$ π$^{−}$, which is required to have an invariant mass within 100 MeV/c$^{2}$ of the known K$^{*}$(892)$^{0}$ mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of about 3 fb$^{−1}$, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The ratio is measured in two regions of the dilepton invariant mass squared, q$^{2}$, to be $ {R}_{K^{*0}}=\left\{\begin{array}{l}{0.66_{-}^{+}}_{0.07}^{0.11}\left(\mathrm{stat}\right)\pm 0.03\left(\mathrm{syst}\right)\kern1em \mathrm{f}\mathrm{o}\mathrm{r}\kern1em 0.045<{q}^2<1.1\kern0.5em {\mathrm{GeV}}^2/{c}^4,\hfill \\ {}{0.69_{-}^{+}}_{0.07}^{0.11}\left(\mathrm{stat}\right)\pm 0.05\left(\mathrm{syst}\right)\kern1em \mathrm{f}\mathrm{o}\mathrm{r}\kern1em 1.1<{q}^2<6.0\kern0.5em {\mathrm{GeV}}^2/{c}^4.\hfill \end{array}\right. $

Journal ArticleDOI
TL;DR: This review provides an overview of the strategies available for a specific targeting of LSECs and presents a detailed analysis of the technical aspects relevant for LSEC analysis including the markers these cells express, the available cell lines and the transgenic mouse models.

Journal ArticleDOI
TL;DR: In this article, the authors report world averages of measurements of b-hadron, c-, c-, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011.
Abstract: This article reports world averages of measurements of b-hadron, c-hadron, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011. In some cases results available in the early part of 2012 are included. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, CP violation parameters, parameters of semileptonic decays and CKM matrix elements.

Journal ArticleDOI
25 Apr 2017-JAMA
TL;DR: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality and potential diagnostic criteria for MINS was found.
Abstract: Importance Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). Objective To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). Design, Setting, and Participants Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. Exposures Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. Main Outcomes and Measures A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. Results Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT Conclusions and Relevance Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Journal ArticleDOI
TL;DR: Data Release 13 (DR13) as discussed by the authors provides the first 1390 spatially resolved integral field unit observations of nearby galaxies from the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS).
Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in 2014 July. It pursues three core programs: the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS). As well as its core program, eBOSS contains two major subprograms: the Time Domain Spectroscopic Survey (TDSS) and the SPectroscopic IDentification of ERosita Sources (SPIDERS). This paper describes the first data release from SDSS-IV, Data Release 13 (DR13). DR13 makes publicly available the first 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA. It includes new observations from eBOSS, completing the Sloan Extended QUasar, Emission-line galaxy, Luminous red galaxy Survey (SEQUELS), which also targeted variability-selected objects and X-ray-selected objects. DR13 includes new reductions of the SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification, and new reductions of the SDSS-III APOGEE-1 data, improving stellar parameters for dwarf stars and cooler stars. DR13 provides more robust and precise photometric calibrations. Value-added target catalogs relevant for eBOSS, TDSS, and SPIDERS and an updated red-clump catalog for APOGEE are also available. This paper describes the location and format of the data and provides references to important technical papers. The SDSS web site, http://www.sdss.org, provides links to the data, tutorials, examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ∼6 yr operations of SDSS-IV.

Journal ArticleDOI
TL;DR: This paper provides a theoretical study of the permutation importance measure for an additive regression model and motivates the use of the recursive feature elimination (RFE) algorithm for variable selection in this context.
Abstract: This paper is about variable selection with the random forests algorithm in presence of correlated predictors. In high-dimensional regression or classification frameworks, variable selection is a difficult task, that becomes even more challenging in the presence of highly correlated predictors. Firstly we provide a theoretical study of the permutation importance measure for an additive regression model. This allows us to describe how the correlation between predictors impacts the permutation importance. Our results motivate the use of the recursive feature elimination (RFE) algorithm for variable selection in this context. This algorithm recursively eliminates the variables using permutation importance measure as a ranking criterion. Next various simulation experiments illustrate the efficiency of the RFE algorithm for selecting a small number of variables together with a good prediction error. Finally, this selection algorithm is tested on the Landsat Satellite data from the UCI Machine Learning Repository.

Journal ArticleDOI
TL;DR: In this article, a review summarizes how insights from mesoscopic scattering theory have direct relevance for optical wave control experiments and vice versa, and the results are expected to have an impact on a number of fields ranging from biomedical imaging to nanophotonics, quantum information, and communication technology.
Abstract: Wave front shaping, the ability to manipulate light fields both spatially and temporally, in complex media is an emerging field with many applications. This review summarizes how insights from mesoscopic scattering theory have direct relevance for optical wave control experiments and vice versa. The results are expected to have an impact on a number of fields ranging from biomedical imaging to nanophotonics, quantum information, and communication technology.

Journal ArticleDOI
TL;DR: The intimate connection between autophagy, mitophagy and cardiovascular disorders is discussed and pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions.
Abstract: Autophagy contributes to the maintenance of intracellular homeostasis in most cells of cardiovascular origin, including cardiomyocytes, endothelial cells, and arterial smooth muscle cells Mitophagy is an autophagic response that specifically targets damaged, and hence potentially cytotoxic, mitochondria As these organelles occupy a critical position in the bioenergetics of the cardiovascular system, mitophagy is particularly important for cardiovascular homeostasis in health and disease Consistent with this notion, genetic defects in autophagy or mitophagy have been shown to exacerbate the propensity of laboratory animals to spontaneously develop cardiodegenerative disorders Moreover, pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions, such as myocardial infarction, various types of cardiomyopathy, and atherosclerosis In this review, we discuss the intimate connection between autophagy, mitophagy, and cardiovascular disorders

Journal ArticleDOI
TL;DR: Recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options, and knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.

Journal ArticleDOI
TL;DR: The Southampton Guidelines have amalgamated the available evidence and a wealth of experts’ knowledge taking in consideration the relevant stakeholders’ opinions and complying with the international methodology standards.
Abstract: Objective:The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery.Background:The exponential growth of laparoscopic liver surgery in recent

Journal ArticleDOI
TL;DR: The reconstruction of deep metazoan relationships using a 1,719-gene dataset with dense taxonomic sampling of non-bilaterian animals that was assembled using a semi-automated procedure, designed to reduce known error sources outperforms previous metazoa gene superalignments in terms of data quality and quantity.

Journal ArticleDOI
Roel Aaij1, Bernardo Adeva2, Marco Adinolfi3, Ziad Ajaltouni4  +813 moreInstitutions (52)
TL;DR: In this article, a doubly charmed baryon Ξcc++ was observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV.
Abstract: A highly significant structure is observed in the Λc+K-π+π+ mass spectrum, where the Λc+ baryon is reconstructed in the decay mode pK-π+. The structure is consistent with originating from a weakly decaying particle, identified as the doubly charmed baryon Ξcc++. The difference between the masses of the Ξcc++ and Λc+ states is measured to be 1334.94±0.72(stat.)±0.27(syst.) MeV/c2, and the Ξcc++ mass is then determined to be 3621.40±0.72(stat.)±0.27(syst.)±0.14(Λc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Λc+ mass. The state is observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.7 fb-1, and confirmed in an additional sample of data collected at 8 TeV.