Université Paris-Est Créteil

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. METHODS: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).

The environmental conditions of Earth, including the climate, are determined by physical, chemical, biological, and human interactions that transform and transport materials and energy. This is the "Earth system": a highly complex entity characterized by multiple nonlinear responses and thresholds, with linkages between disparate components. One important part of this system is the iron cycle, in which iron-containing soil dust is transported from land through the atmosphere to the oceans, affecting ocean biogeochemistry and hence having feedback effects on climate and dust production. Here we review the key components of this cycle, identifying critical uncertainties and priorities for future research.

Position Papers1 October 1985Proposed Revised Criteria for the Classification of Acute Myeloid LeukemiaA Report of the French-American-British Cooperative GroupJOHN M. BENNETT, M.D., DANIEL CATOVSKY, M.D., MARIE T. DANIEL, M.D., GEORGE FLANDRIN, M.D., DAVID A. G. GALTON, M.D., HARVEY R. GRALNICK, M.D., CLAUDE SULTAN, M.D.JOHN M. BENNETT, M.D.Search for more papers by this author, DANIEL CATOVSKY, M.D.Search for more papers by this author, MARIE T. DANIEL, M.D.Search for more papers by this author, GEORGE FLANDRIN, M.D.Search for more papers by this author, DAVID A. G. GALTON, M.D.Search for more papers by this author, HARVEY R. GRALNICK, M.D.Search for more papers by this author, CLAUDE SULTAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-4-620 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe first proposals for the morphologic classification of the acute leukemias by the French-American-British (FAB) group (1) were put forward in the hope that they might serve as a basis for a generally acceptable system of classification. Such a system would permit comparisons between series of cases, show prognostic differences between different categories, and provide a framework of reference for persons working in different biological disciplines who use material from patients with leukemia.In the last 7 years the FAB proposals have been accepted by many groups involved in cooperative clinical trials with both acute myeloid leukemia and acute lymphoblastic...References1. BENNETTCATOVSKYDANIEL JDM. Proposals for the classification of the acute leukaemias: French-American-British Cooperative Group. Br J Haematol. 1976;33:451-8. CrossrefMedlineGoogle Scholar2. SECOND INTERNATIONAL WORKSHOP ON CHROMOSOMES IN LEUKEMIA, 1979. Morphological analysis of acute promyelocytic (M3) and t(8;21). Cancer Genet Cytogenet. 1980;2:97-8. CrossrefGoogle Scholar3. THIRD INTERNATIONAL WORKSHOP ON CHROMOSOMES IN LEUKEMIA, 1980. Clinical significance of chromosomal abnormalities in acute lymphoblastic leukemia. 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Hypocellular acute leukemia. Am J Med. 1982;72:391-5. CrossrefMedlineGoogle Scholar31. CATOVSKYDECARDULLOO'BRIEN DSLM. Cytochemical markers of differentiation in acute leukemia. Cancer Res. 1981;41( 11 pt 2):4824-32. MedlineGoogle Scholar32. PARKINARTHURABRAMSON JDC. Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics. Blood. 1983;119:1321-31. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, New York; London England Paris and Creteil France Bethesda Maryland▸From the University of Rochester Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York; Medical Research Council Leukaemia Unit, Royal Postgraduate Medical School, London, England; Institut de Recherches sur les Leucemies et les Maladies du Sang, Hopital Saint-Louis, Paris, France; Hematology Service, National Institutes of Health, Bethesda, Maryland; and Service Central d'Hematologie-Immunologie, Hopital Henri Mondor, Creteil, France. 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Prediction of Cytogenetically Normal Acute Myeloid Leukemia Based on a Gene Expression ModelReferencesCell signaling pathways as molecular targets to eliminate AML stem cellsIntensive versus less-intensive antileukemic therapy in older adults with acute myeloid leukemia: A systematic reviewNovel therapeutic targets for chronic myelomonocytic leukemiaControversies in the recent (2016) World Health Organization classification of acute myeloid leukemiaCharacteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study*Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A AxisShort loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networksGenomic Landscape and Clonal Evolution of AMLManagement of Acute Promyelocytic LeukemiaLeukemia cutis in a medical center in southern Taiwan: A retrospective study of 42 patientsNext-generation sequencing reveals gene mutations landscape and clonal evolution in patients with acute myeloid leukemiaAssociation of kinesin family member 2A with increased disease risk, deteriorative clinical characteristics, and shorter survival profiles in acute myeloid leukemiaTrdmt1 3'-untranslated region functions as a competing endogenous RNA in leukemia HL-60 cell differentiationDisseminated intravascular coagulopathy in non-promyelocytic acute myeloid leukemia: Incidence, clinical and laboratory features and prognostic significanceAcute erythroid leukemia is enriched in NUP98 fusions: a report from the Children’s Oncology GroupGene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemiaReductive regulation of BECN1 gene in adult Egyptian patients with do novo AMLSecondary chronic myeloid leukemia following acute myeloid leukemia treated with autologous hematopoietic stem cell transplantation: a case reportDelineation of target expression profiles in CD34+/CD38− and CD34+/CD38+ stem and progenitor cells in AML and CMLEarly Mortality in Children and Adolescents with Acute Promyelocytic Leukemia: Experience of the Boldrini Children’s CenterP‐glycoprotein and multidrug resistance‐associated protein‐1 expression in acute myeloid leukemia: Biological and prognosis implicationsOutcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide—an International Collaborative StudyFc gamma receptor expression serves as prognostic and diagnostic factor in AMLOverexpression of long noncoding RNA HOXA‐AS2 predicts an adverse prognosis and promotes tumorigenesis via SOX4/PI3K/AKT pathway in acute myeloid leukemiaCD105 (endoglin) as risk marker in AML patients undergoing stem cell transplantationWT1, PRAME, and PR3 mRNA Expression in Acute Myeloid Leukemia (AML)Çukurova Bölgesinde akut lenfoblastik lösemili çocuklarda vasküler endotelyal büyüme faktörü (VEGF-C) ve temel fibroblast büyüme faktörü (bFGF) plazma ekspresyonu ve metilasyon seviyeleriCutaneous Myeloid Sarcoma Mimicking Skin Cancer in Aleukemic Patients: a Diagnostic Challenge in SurgeryCritical Upper Airway Obstruction as the First Symptom of Acute Myeloid Leukemia—An Anesthesiologic ReminderNormal myeloid progenitor cell subset-associated gene signatures for acute myeloid leukaemia subtyping with prognostic impactHarlequin cell: Ubiquitous or pathognomic?Intravoxel Incoherent Motion Diffusion-weighted MRI of Infiltrated Marrow for Predicting Overall Survival in Newly Diagnosed Acute Myeloid LeukemiaIdentification of CD318 (CDCP1) as novel prognostic marker in AMLPeripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemiaModifications of H3K4 methylation levels are associated with DNA hypermethylation in acute myeloid leukemiaA‐kinase interacting protein 1 might serve as a novel biomarker for worse prognosis through the interaction of chemokine (C‐X‐C motif) ligand 1/chemokine (C‐X‐C motif) ligand 2 in acute myeloid leukemiaCorrelation of miR‐181a and three HOXA genes as useful biomarkers in acute myeloid leukemiaAcute Leukemia of Myeloid, Lymphoid, and Ambiguous Lineage and Related MalignanciesCytogenetics/cytogenomicsAcute leukemiasIsotretinoin is active in the initial management of acute pro-myelocytic leukemiaThe power and potential of integrated diagnostics in acute myeloid leukaemia <em>Circ_0002232</em> Acts as a Potential Biomarker for AML and Reveals a Potential ceRNA Network of <em>Circ_0002232</em>/<em>miR-92a-3p</em>/<em>PTEN</em> Anti-leukemic effects of simvastatin on NRASG12D mutant acute myeloid leukemia cellsCD105 (Endoglin) as negative prognostic factor in AMLAssociations of PGK1 promoter hypomethylation and PGK1-mediated PDHK1 phosphorylation with cancer stage and prognosis: a TCGA pan-cancer analysisChronic Myelomonocytic Leukemia: Insights into Biology, Prognostic Factors, and TreatmentHuman-level recognition of blast cells in acute myeloid leukaemia with convolutional neural networksDOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemiaCytogenetic profile of a representative cohort of young adults with de novo acute myéloblastic leukaemia in MoroccoThe Mechanism of Anti–PD-L1 Antibody Efficacy against PD-L1–Negative Tumors Identifies NK Cells Expressing PD-L1 as a Cytolytic EffectorPriming with GM-CSF instead of G-CSF enhances CAG-induced apoptosis of acute monocytic leukemia cells in vitroSerous retinal detachment as an initial presentation of childhood acute myeloid leukemiaKnockdown of Long Noncoding RNA Plasmacytoma Variant Translocation 1 with Antisense Locked Nucleic Acid GapmeRs Exerts Tumor-Suppressive Functions in Human Acute Erythroleukemia Cells Through Downregulation of C-MYC ExpressionNot Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome StudiesAssociation of Leukemia Cutis With Survival in Acute Myeloid LeukemiaThe Neuropilin-1 Ligand, Sema3A, Acts as a Tumor Suppressor in the Pathogenesis of Acute LeukemiaFeline Leukaemia Virus Associated with Leukaemia in Cats in Santa Catarina, BrazilDynamic changes in the level of WT1 as an MRD marker to predict the therapeutic outcome of patients with AML with and without allogeneic stem cell transplantationChronic Myelomonocytic Leukemia: 2018 Update to Prognosis and TreatmentMicroRNA-335/ID4 dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemiaCircular RNA of vimentin expression as a valuable predictor for acute myeloid leukemia development and prognosisCanonical WNT Signaling Pathway is Altered in Mesenchymal Stromal Cells From Acute Myeloid Leukemia Patients And Is Implicated in BMP4 Down-RegulationGenomic subtyping and therapeutic targeting of acute erythroleukemiaPrognostic Value of Genetic Alterations in Elderly Patients with Acute Myeloid Leukemia: A Single Institution ExperienceMutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on next‑generation sequencingACUTE MYELOID LEUKAEMIA, MIXED PHENOTYPE ACUTE LEUKAEMIA, THE MYELODYSPLASTIC SYNDROMES AND HISTIOCYTIC NEOPLASMSIdentification of novel serum biomarker for the detection of acute myeloid leukemia based on liquid chromatography-mass spectrometryWheat Germ Agglutinin as a Potential Therapeutic Agent for LeukemiaMicroRNA expression profiles discriminate childhood T‐ from B‐acute lymphoblastic leukemiaComparison of Peripheral Blast Clearance and Day 14 Bone Marrow Biopsy in Predicting Remission Status and Survival After 7+3 Induction in Acute Myeloid LeukemiaAdditional prognostic impact of the percentage of erythroid cells in the bone marrow of patients with myelodysplastic syndromesPreliminary study on the role of miR‑148a and DNMT1 in the pathogenesis of acute myeloid leukemiaAcute Myeloid Leukemia: An UpdateAllogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid LeukemiaRate of differentiation syndrome in patients based on timing of initial all-trans retinoic acid administrationAnxiety and depression predict unfavorable survival in acute myeloid leukemia patientsAcute Monoblastic Leukemia with t(11;17)(q23;q21): Fusion of the KMT2A ( MLL ) and MLLT6 ( AF17 ) GenesAcute myeloid leukemia with t(16;16)(p13.1;q22)/CBFB-MYH11Current Management and Recent Advances in the Treatment of Chronic Myelomonocytic LeukemiaMaintenance Therapy With Interleukin-2 for Childhood AMLNext-generation sequencing-based genetic landscape and its clinical implications for Chinese acute myeloid leukemia patientsDysregulation of miR-200s clusters as potential prognostic biomarkers in acute myeloid leukemiaCurrent status and trends in the diagnostics of AML and MDSIdentification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemiaExpression Analysis of PVT1 , CCDC26, and CCAT1 Long Noncoding RNAs in Acute Myeloid Leukemia PatientsIncreased Survival for Children With Acute Myeloid Leukemia Results From Improved Postrelapse TreatmentGenital ulcers as diagnostic clue for acute myeloid leukaemiaHexosamine Biosynthetic Pathway Inhibition Leads to AML Cell Differentiation and Cell DeathClinical diagnosis of adult patients with acute megakaryocytic leukemiaIMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AMLTSC gene expression in the newly diagnosed Egyptian acute leukemia patientsMicroRNA‐9 suppresses cancer proliferation and cell in acute lymphoblastic leukemia with of expression is a potential prognostic and biomarker in cytogenetically normal acute myeloid leukemiaKnockdown of suppresses of AML by through the 2 as an Prognostic in Acute Myeloid in Acute Myeloid of Genetic Analysis in New of Acute Myeloid mutations in Chinese patients with acute myeloid leukemia and myelodysplastic Expression of Long Noncoding RNA Is Associated with Prognosis in Acute Myeloid Leukemia 1 an Prognosis in Egyptian Patients with Acute Myeloid of Adolescents and With Acute Myeloid Leukemia in a Single and outcome of in acute myeloid leukemia patients in a medical center in in de novo acute myeloid analysis according to the risk by in adult acute myeloid leukemia patients treated in the Leukemia Study of of cell differentiation in human myeloid and levels in bone marrow and with the survival rate of patients childhood acute lymphoblastic profiles blast cytogenetic risk mutations and therapy response in acute myeloid gene with a percentage of leukemic blasts in de novo acute myeloid IN and Treatment of Acute Myeloid Leukemia in of and Myeloid Myeloid LeukemiaA study of in patients with myelodysplastic and to acute myeloid Expression of Is with and in Acute Myeloid of outcome 2 in children with acute myeloid expression of acute myeloid leukemia from adult patients with and through and in the impact of a karyotype in impact of and expression levels in treated adult acute myeloid leukemia analysis of diagnosed de novo adult acute erythroid leukemia patients following the to World Health Organization expression on AML blasts expression of is associated with poor clinical outcome in acute myeloid leukemiaCharacteristics and outcome of patients with acute promyelocytic leukemia treated with or without arsenic years of the Proposals for the classification of chronic and and levels in myeloid leukemia: a and as a predictor of for patients with acute myeloid leukemia treated with cytarabine and and prognostic significance of eosinophilia and in acute myelomonocytic leukemia acute leukemia: of the classification and in leukaemia system acute myeloid leukemia into for dysregulation of predicts disease and outcome in myeloid of Expression by to and a Prognosis in Acute Promyelocytic Leukemia of acute myeloid leukemias reveals novel bone marrow blasts from outcome prediction in myelodysplastic and a of the risk of the Revised International Prognostic of Expression in Acute Myeloid marrow for diagnosis and of acute myeloid leukemiaThe in acute myeloid leukemia at diagnosis in to clinical disease of Mesenchymal Cells from a of AML Patients a to Treatment hypomethylation of gene in the bone marrow of patients with acute myeloid of FAB classification on outcome in acute myeloid leukemia, patients undergoing allogeneic stem cell in An analysis of patients from the acute leukemia working of of cytogenetic classification and MRD status with outcome of autologous versus allogeneic stem cell in adults with primary acute myeloid leukemia in first expression predicts adverse prognosis in cytogenetically normal acute myeloid leukemiaThe of and the Morphological Classification of Acute and the of is associated with poor outcome in de novo acute myeloid of Acute Promyelocytic and promoter methylation is associated with acute myeloid leukemia in a Acute promyelocytic leukaemia is among acute myeloid in a cancer study from to and Prognosis of of Acute of acute myeloid leukemia in level with in of acute myeloid leukemia 2 expression in de novo acute myeloid leukemia of and Cell in Health and sequencing and mutations in acute erythroid of molecular mutations in acute myeloid Mutations and in Cytogenetically Normal Acute Myeloid expression clinical outcome in acute myeloid leukemia with normal in and to Acute Myeloid Leukemia in disease detection in lymphoblastic leukemia based on gene of inversion 16 in chronic myeloid leukaemia in blast in by biological features and outcome with myelodysplastic with a for its into of myelodysplastic of and in of on blasts in patients with acute myeloid leukemia with of and its ligand on blasts with prognosis of patients with of leukemic stem cells mutations of 1 and 2 are prognostic and markers in patients with acute myeloid leukaemia with normal myeloid leukemia in the study of clinical and biological features and results of the at the of Clinical in the of adult acute myeloid status and and and serve as novel

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

A preoperative computed tomography (CT) scan grading muscular fatty degeneration in five stages was done in 63 patients scheduled for repair of a torn rotator cuff. The results were compared with postoperative evaluation done after a mean of 17.7 months in 57 patients. Postoperative arthrographies were also performed in 56 patients. Preoperative CT scans demonstrated that infraspinatus fatty degeneration can occur in the presence of large anterosuperior tears even when the infraspinatus tendon is not torn; it worsens with time. The subscapularis rarely degenerates, and when it does it degenerates moderately, even when its tendon is not torn. After an effective surgical repair, moderate supraspinatus degeneration regressed in six of 14 patients; that of the infraspinatus never regressed but rather, increased, in three patients. One of these deteriorations, involving both supra- and infraspinatus, could probably be attributed to a partial subscapular nerve injury. Infraspinatus degeneration was correlated with functional pre- and postoperative impairment of active external rotation. Recurrence of infraspinatus tear was never observed, but recurrence occurred in 25% of supraspinatus repairs. Infraspinatus degeneration had a highly negative influence on the outcome of supraspinatus repairs. It seems preferable to operate on wide tears before irreversible muscular damage takes place.

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition.

The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic alpha helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 alpha helix and, in particular, on a triad of p53 amino acids-Phe19, Trp23, and Leu26-which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic alpha helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

A preoperative computed tomography (CT) scan grading muscular fatty degeneration in five stages was done in 63 patients scheduled for repair of a torn rotator cuff. The results were compared with postoperative evaluation done after a mean of 17.7 months in 57 patients. Postoperative arthrographies were also performed in 56 patients. Preoperative CT scans demonstrated that infraspinatus fatty degeneration can occur in the presence of large anterosuperior tears even when the infraspinatus tendon is not torn; it worsens with time. The subscapularis rarely degenerates, and when it does it degenerates moderately, even when its tendon is not torn. After an effective surgical repair, moderate supraspinatus degeneration regressed in six of 14 patients; that of the infraspinatus never regressed but rather, increased, in three patients. One of these deteriorations, involving both supra- and infraspinatus, could probably be attributed to a partial subscapular nerve injury. Infraspinatus degeneration was correlated with functional pre- and postoperative impairment of active external rotation. Recurrence of infraspinatus tear was never observed, but recurrence occurred in 25% of supraspinatus repairs. Infraspinatus degeneration had a highly negative influence on the outcome of supraspinatus repairs. It seems preferable to operate on wide tears before irreversible muscular damage takes place.

BACKGROUND: Public health recommendations and governmental measures during the COVID-19 pandemic have resulted in numerous restrictions on daily living including social distancing, isolation and home confinement. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on health behaviours and lifestyles at home is undefined. Therefore, an international online survey was launched in April 2020, in seven languages, to elucidate the behavioural and lifestyle consequences of COVID-19 restrictions. This report presents the results from the first thousand responders on physical activity (PA) and nutrition behaviours. METHODS: Following a structured review of the literature, the "Effects of home Confinement on multiple Lifestyle Behaviours during the COVID-19 outbreak (ECLB-COVID19)" Electronic survey was designed by a steering group of multidisciplinary scientists and academics. The survey was uploaded and shared on the Google online survey platform. Thirty-five research organisations from Europe, North-Africa, Western Asia and the Americas promoted the survey in English, German, French, Arabic, Spanish, Portuguese and Slovenian languages. Questions were presented in a differential format, with questions related to responses "before" and "during" confinement conditions. RESULTS: 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%) were included in the analysis. The COVID-19 home confinement had a negative effect on all PA intensity levels (vigorous, moderate, walking and overall). Additionally, daily sitting time increased from 5 to 8 h per day. Food consumption and meal patterns (the type of food, eating out of control, snacks between meals, number of main meals) were more unhealthy during confinement, with only alcohol binge drinking decreasing significantly. CONCLUSION: While isolation is a necessary measure to protect public health, results indicate that it alters physical activity and eating behaviours in a health compromising direction. A more detailed analysis of survey data will allow for a segregation of these responses in different age groups, countries and other subgroups, which will help develop interventions to mitigate the negative lifestyle behaviours that have manifested during the COVID-19 confinement.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Macrophages (MPs) are important for skeletal muscle regeneration in vivo and may exert beneficial effects on myogenic cell growth through mitogenic and antiapoptotic activities in vitro. However, MPs are highly versatile and may exert various, and even opposite, functions depending on their activation state. We studied monocyte (MO)/MP phenotypes and functions during skeletal muscle repair. Selective labeling of circulating MOs by latex beads in CX3CR1(GFP/+) mice showed that injured muscle recruited only CX3CR1(lo)/Ly-6C(+) MOs from blood that exhibited a nondividing, F4/80(lo), proinflammatory profile. Then, within muscle, these cells switched their phenotype to become proliferating antiinflammatory CX3CR1(hi)/Ly-6C(-) cells that further differentiated into F4/80(hi) MPs. In vitro, phagocytosis of muscle cell debris induced a switch of proinflammatory MPs toward an antiinflammatory phenotype releasing transforming growth factor beta1. In co-cultures, inflammatory MPs stimulated myogenic cell proliferation, whereas antiinflammatory MPs exhibited differentiating activity, assessed by both myogenin expression and fusion into myotubes. Finally, depletion of circulating MOs in CD11b-diphtheria toxin receptor mice at the time of injury totally prevented muscle regeneration, whereas depletion of intramuscular F4/80(hi) MPs at later stages reduced the diameter of regenerating fibers. In conclusion, injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth.

We present the global general circulation model IPSL-CM5 developed to study the long-term response of the climate system to natural and anthropogenic forcings as part of the 5th Phase of the Coupled Model Intercomparison Project (CMIP5). This model includes an interactive carbon cycle, a representation of tropospheric and stratospheric chemistry, and a comprehensive representation of aerosols. As it represents the principal dynamical, physical, and bio-geochemical processes relevant to the climate system, it may be referred to as an Earth System Model. However, the IPSL-CM5 model may be used in a multitude of configurations associated with different boundary conditions and with a range of complexities in terms of processes and interactions. This paper presents an overview of the different model components and explains how they were coupled and used to simulate historical climate changes over the past 150 years and different scenarios of future climate change. A single version of the IPSL-CM5 model (IPSL-CM5A-LR) was used to provide climate projections associated with different socio-economic scenarios, including the different Representative Concentration Pathways considered by CMIP5 and several scenarios from the Special Report on Emission Scenarios considered by CMIP3. Results suggest that the magnitude of global warming projections primarily depends on the socio-economic scenario considered, that there is potential for an aggressive mitigation policy to limit global warming to about two degrees, and that the behavior of some components of the climate system such as the Arctic sea ice and the Atlantic Meridional Overturning Circulation may change drastically by the end of the twenty-first century in the case of a no climate policy scenario. Although the magnitude of regional temperature and precipitation changes depends fairly linearly on the magnitude of the projected global warming (and thus on the scenario considered), the geographical pattern of these changes is strikingly similar for the different scenarios. The representation of atmospheric physical processes in the model is shown to strongly influence the simulated climate variability and both the magnitude and pattern of the projected climate changes.

SymPy is an open source computer algebra system written in pure Python. It is built with a focus on extensibility and ease of use, through both interactive and programmatic applications. These characteristics have led SymPy to become a popular symbolic library for the scientific Python ecosystem. This paper presents the architecture of SymPy, a description of its features, and a discussion of select submodules. The supplementary material provide additional examples and further outline details of the architecture and features of SymPy.

) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.