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1. Ecology and larval population dynamics of the primary malaria vector Nyssorhynchus darlingi in a high transmission setting dominated by fish farming in western Amazonian Brazil

Author

Samir Moura Kadri, Catharine Prussing, Jan E. Conn, Paulo Rufalco-Moutinho, Gabriel Carrasco-Escobar, Marta Moreno, Joseph M. Vinetz, Maria Anice Mureb Sallum, Diego Peres Alonso, Paulo Eduardo Martins Ribolla, Dionicia Gamboa, Universidade Estadual Paulista (Unesp), London Sch Hyg & Trop Med, Univ Peruana Cayetano Heredia, SUNY Albany, Wadsworth Ctr, Yale Sch Med, Universidade de São Paulo (USP), and Universidade de Brasília (UnB)

Subjects
0301 basic medicine, Life Cycles, Plasmodium, Population Dynamics, Aquaculture, Disease Vectors, Population density, Mosquitoes, Geographical locations, 0302 clinical medicine, Larvae, Medical Conditions, Mathematical and Statistical Techniques, Abundance (ecology), Dry season, Medicine and Health Sciences, education.field_of_study, Multidisciplinary, Ecology, Statistics, Eukaryota, Agriculture, Insects, Infectious Diseases, Larva, Vertebrates, Physical Sciences, Medicine, Seasons, Fish Farming, purl.org/pe-repo/ocde/ford#3.03.06 [https], Brazil, Research Article, Wet season, Arthropoda, Fish farming, Science, 030231 tropical medicine, Population, Fisheries, Mosquito Vectors, Biology, Research and Analysis Methods, Amphibians, 03 medical and health sciences, Anopheles, Parasite Groups, parasitic diseases, medicine, Parasitic Diseases, Animals, Statistical Methods, education, Ponds, Organisms, Biology and Life Sciences, South America, medicine.disease, Tropical Diseases, Invertebrates, Malaria, Insect Vectors, Species Interactions, 030104 developmental biology, Fish, Multivariate analysis, Vector (epidemiology), Multivariate Analysis, Parasitology, People and places, Zoology, Apicomplexa, Entomology, Mathematics, Developmental Biology
Abstract

Made available in DSpace on 2021-06-25T15:01:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-08 US National Institutes of Health ICEMR Tropical Disease Research-WHO Contract Vale do Rio Jurua in western Acre, Brazil, is a persistent malaria transmission hotspot partly due to fish farming development that was encouraged to improve local standards of living. Fish ponds can be productive breeding sites for Amazonian malaria vector species, including Nyssorhynchus darlingi, which, combined with high human density and mobility, add to the local malaria burden.This study reports entomological profile of immature and adult Ny. darlingi at three sites in Mancio Lima, Acre, during the rainy and dry season (February to September, 2017). From 63 fishponds, 10,859 larvae were collected, including 5,512 first-instar Anophelinae larvae and 4,927 second, third and fourth-instars, of which 8.5% (n = 420) were Ny. darlingi. This species was most abundant in not-abandoned fishponds and in the presence of emerging aquatic vegetation. Seasonal analysis of immatures in urban landscapes found no significant difference in the numbers of Ny. darlingi, corresponding to equivalent population density during the rainy to dry transition period. However, in the rural landscape, significantly higher numbers of Ny. darlingi larvae were collected in August (IRR = 5.80, p = 0.037) and September (IRR = 6.62, p = 0.023) (dry season), compared to February (rainy season), suggesting important role of fishponds for vector population maintenance during the seasonal transition in this landscape type. Adult sampling detected mainly Ny. darlingi (similar to 93%), with similar outdoor feeding behavior, but different abundance according to landscape profile: urban site 1 showed higher peaks of human biting rate in May (46 bites/person/hour), than February (4) and September (15), while rural site 3 shows similar HBR during the same sampling period (22, 24 and 21, respectively). This study contributes to a better understanding of the larvae biology of the main malaria vector in the Vale do Rio Jurua region and, ultimately will support vector control efforts. Univ Estadual Paulista, Inst Biociencias Botucatu, Dept Bioestat Biol Vegetal Parasitol & Zool, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biotecnol, Botucatu, SP, Brazil London Sch Hyg & Trop Med, Dept Infect Biol, London, England Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab ICEMR Amazonia, Labs Invest & Desarrollo, Lima, Peru SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru Univ Peruana Cayetano Heredia, Inst Med Trop Alexander Humboldt, Lima, Peru Yale Sch Med, Dept Internal Med, Sect Infect Dis, New Haven, CT USA Univ Sao Paulo, Fac Saude Publ, Dept Epidemiol, Sao Paulo, Brazil Univ Brasilia, Nucleo Med Trop, Brasilia, DF, Brazil Univ Estadual Paulista, Inst Biociencias Botucatu, Dept Bioestat Biol Vegetal Parasitol & Zool, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biotecnol, Botucatu, SP, Brazil US National Institutes of Health ICEMR: U19 AI089681 Tropical Disease Research-WHO Contract: 201460655

Published
2021

2. Autochthonous leprosy in Spain: Has the transmission of Mycobacterium leprae stopped?

Author

Diana Gómez-Barroso, Inés Suárez-García, Paul E. M. Fine, FIIB HUIS HHEN, [Suarez-Garcia, Ines] Hosp Univ Infanta Sofia, Dept Internal Med, FIIB HUIS HHEN, Infect Dis Grp, Madrid, Spain., [Suarez-Garcia, Ines] Univ Europea, Fac Ciencias Biomed & Salud, Madrid, Spain., [Gomez-Barroso, Diana] Inst Salud Carlos III, Ctr Nacl Epidemiol, CIBERESP CIBER Epidemiol & Salud Publ, Madrid, Spain., and [Fine, Paul E. M.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London, England.

Subjects
Bacterial Diseases, Male, Epidemiology, España, RC955-962, Population Dynamics, Age at diagnosis, Geographical locations, law.invention, Medical Conditions, law, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Patterns, Mycobacterium leprae, Travel, biology, Geography, Incidence (epidemiology), Incidence, Age Factors, Middle Aged, Mycobacterium Leprae, Europe, Actinobacteria, Autochthonous Transmission, Lepra, Infectious Diseases, Transmission (mechanics), Female, Leprosy, Public aspects of medicine, RA1-1270, Lepra [enfermedad de Hansen] (A30 ), Brazil, Research Article, Neglected Tropical Diseases, Adult, Infectious Disease Epidemiology, Sex Factors, Decline, medicine, Humans, European Union, Aged, Bacteria, Population Biology, Imported leprosy, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, South America, Tropical Diseases, biology.organism_classification, medicine.disease, Clinical type, Geographic Distribution, Eastern mediterranean, Spain, People and places, Trends, Demography
Abstract

Background The aim of this study is to explore whether transmission of M. leprae has ceased in Spain, based upon the patterns and trends of notified cases. Methodology Data on new cases reported to the National Leprosy Registry between the years 2003–2018 were extracted. In absence of detailed travel history, cases were considered “autochthonous” or “imported” based on whether they were born within or outside of Spain. These data were analyzed by age, sex, clinical type, country of origin, and location of residence at time of notification. Principal findings Data were available on 61 autochthonous and 199 imported cases since 2003. There were clear declines in incidence in both groups, and more imported than autochthonous cases every year since 2006. Autochthonous cases were more frequently multibacillary and had older age at diagnosis compared to imported cases. All the autochthonous cases had been born before 1985 and were more than 25 years old at diagnosis. Male-to-female ratio increased with time for autochthonous cases (except for the last time period). The imported cases originated from 25 countries, half of them from Brasil and Paraguay. Autochthonous cases were mainly distributed in the traditionally endemic regions, especially Andalucía and the eastern Mediterranean coast. Conclusions Autochthonous and imported cases have different epidemiologic patterns in Spain. There was a clear decline in incidence rates of autochthonous disease, and patterns consistent with those reported from other regions where transmission has ceased. Autochthonous transmission of M. leprae is likely to have now effectively stopped in Spain., Author summary There is increasing interest in the potential for cessation of transmission of M Leprae. In several European countries, as social and economic conditions have improved, leprosy rates have declined and transmission appears to have stopped. The epidemiology of leprosy is still not fully understood: the study of leprosy in countries with low incidence rates can give valuable information on its epidemiology that could inform eradication campaigns in other countries. Leprosy has been endemic in Spain for centuries and, despite very low incidence in the last decades, new autochthonous cases are diagnosed every year. In this study, we analyse the epidemiologic trends of autochthonous leprosy in Spain in recent years. Our data provide insights into the dramatic decline of leprosy in Spain since 1950, and, for the cases diagnosed after 2003, show a shift from a predominace of disease attributable to locally acquired infection to overwhelming predominance of disease attributable to infections acquired elsewhere. The comparison of patterns of disease between the autochthonous and imported cases shows important differences, suggesting that the most recent autochthonous cases were those with long incubation periods after infections which were acquired many years ago. The epidemiologic trends are similar to those found in other countries with declining incidence and suggest that transmission effectively stopped in Spain more than two decades ago.

Published
2020

3. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author

Javier Benitez, Marie Stenmark-Askmalm, Susan L. Neuhausen, Pascal Guénel, Jane Carpenter, Christine B. Ambrosone, Dominique Stoppa-Lyonnet, Nadine Tung, Gad Rennert, Stephen J. Chanock, Andrew K. Godwin, Regina M. Santella, Brita Arver, Karoline Kuchenbaecker, Kamila Czene, Vessela N. Kristensen, Natalia Bogdanova, Nazneen Rahman, Jianjun Liu, Federico Canzian, Hoda Anton-Culver, Maya Ghoussaini, Mark E. Robson, Sue K. Park, Manjeet K. Bolla, Roger L. Milne, Veli-Matti Kosma, Siranoush Manoukian, Angela Cox, Daniel F. Schmidt, Kay-Tee Khaw, Rosario Tumino, Melissa C. Southey, Ramunas Janavicius, Irene Konstantopoulou, Carl Blomqvist, John L. Hopper, Sue Healey, Christine Rappaport, Marco Montagna, SA Gayther, Heather Eliassen, Carolien H.M. van Deurzen, Jacques Simard, Emiel J. Rutgers, Jonine Figueroa, Maria A. Caligo, Volker Arndt, Sylvie Mazoyer, Diana Eccles, M.J. Hooning, Antoinette Hollestelle, Mary B. Daly, Robert Winqvist, Antonis C. Antoniou, Patricia A. Ganz, Orland Diez, Priyanka Sharma, Ana Osorio, Daniel Barrowdale, Loic Le Marchand, Drakoulis Yannoukakos, Elinor J. Sawyer, Conxi Lázaro, Soo-Hwang Teo, Penny Soucy, Paolo Radice, John W. M. Martens, Steve Ellis, David E. Goldgar, Anna Jakubowska, Maria Kabisch, Raymonda Varon-Mateeva, Diether Lambrechts, Paul D.P. Pharoah, Leigha Senter, Anna González-Neira, Cecilia M. Dorfling, Brian E. Henderson, Rulla M. Tamimi, Sara Margolin, Susan M. Gapstur, Ian Tomlinson, Thérèse Truong, Robert A.E.M. Tollenaar, Amanda E. Toland, Anna Marie Mulligan, Irene L. Andrulis, Isabelle Romieu, Monica Barile, Florentia Fostira, Johanna Rantala, Enes Makalic, Eitan Friedman, Zhaoming Wang, Mark H. Greene, Noralane M. Lindor, Julie M. Cunningham, Riccardo Dolcetti, Steven N. Hart, Mary Beth Terry, Jenny Chang-Claude, Austin Miller, Georgia Chenevix-Trench, Asta Försti, Kathleen E. Malone, Paolo Peterlongo, Lothar Haeberle, Celine M. Vachon, Elizabeth J. van Rensburg, Michael Jones, Laima Tihomirova, Penelope Miron, Eunjung Lee, María José Sánchez, Hatef Darabi, Frans B. L. Hogervorst, Matthias W. Beckmann, Edith Olah, Annika Lindblom, Phuong L. Mai, Emily Hallberg, Alison M. Dunning, Kathleen Claes, Esther M. John, Sofia Khan, David J. Hunter, Kristiina Aittomäki, Katherine L. Nathanson, Lars Beckmann, Stephanie V. Blank, Wei Zheng, Olufunmilayo I. Olopade, Heli Nevanlinna, Miguel de la Hoya, Olga M. Sinilnikova, Bruce Poppe, Catherine M. Phelan, S. Lindstrom, Stig E. Bojesen, Curtis Olswold, Fredrick R. Schumacher, Janet E. Olson, Tuomas Heikkinen, Judy Garber, Fergus J. Couch, Tara M. Friebel, Isabel dos-Santos-Silva, Douglas F. Easton, Song Yao, Dieter Flesch-Janys, Hans Ehrencrona, Simon S. Cross, Rodney J. Scott, Kenneth Offit, Petra H.M. Peeters, Clare Turnbull, Taru A. Muranen, William J. Tapper, Trinidad Caldés, Jenny Lester, Robert L. Nussbaum, Paul A. James, Marike Gabrielson, Susan M. Domchek, Mads Thomassen, Marilie D. Gammon, Susan L. Slager, Graham G. Giles, Silje Nord, Hans Wildiers, Hiltrud Brauch, Gustavo Mendoza-Fandiño, Christopher A. Haiman, Martine Dumont, Mark S. Goldberg, Bernardo Bonanni, Jirong Long, Kyriaki Michailidou, Ute Hamann, Wendy K. Chung, Marc J. Gunter, Mia M. Gaudet, Keith Humphreys, Per Hall, Yuan C. Ding, Simona Agata, Julia A. Knight, Robert Pilarski, Claudine Isaacs, Alvaro A.N. Monteiro, Montserrat Garcia-Closas, Rosa B. Barkardottir, Beth Y. Karlan, Uffe Birk Jensen, Arif B. Ekici, Evgeny N. Imyanitov, Alex Teulé, Anne-Marie Gerdes, Frederik Marme, Debra Frost, Anthony J. Swerdlow, Yon Ko, Xiaohong R. Yang, Jan Lubinski, Peter A. Fasching, Lesley McGuffog, Jacek Gronwald, Katri Pylkäs, Banu Arun, Josef Herzog, Gord Glendon, Doris Steinemann, Tomasz Huzarski, Peter Kraft, Anja Rudolph, Arto Mannermaa, Habibul Ahsan, Christian F. Singer, Rita K. Schmutzler, Julian Peto, Giski Ursin, Shan Wang-Gohrke, Andrea L. Richardson, Jeffrey N. Weitzel, Børge G. Nordestgaard, Marjanka K. Schmidt, Alice S. Whittemore, Hermann Brenner, Barbara Burwinkel, D Thompson, Csilla I. Szabo, M. Pilar Zamora, Janna Lilyquist, Muhammad G. Kibriya, Yael Laitman, Helen Tsimiklis, W. D. Foulkes, Thomas Hansen, Francesca Damiola, Robert N. Hoover, Ava Kwong, Alfons Meindl, Siddhartha Kar, Manuel R. Teixeira, Elisabete Weiderpass, Bernard Peissel, Saundra S. Buys, Peter Devilee, Unión Europea. Comisión Europea. 7 Programa Marco, Cancer Research UK (Reino Unido), National Institutes of Health (Estados Unidos), Canadian Institutes of Health Research, Florida Breast Cancer Foundation (Estados Unidos), Dunning, Alison [0000-0001-6651-7166], Ghoussaini, Maya [0000-0002-2415-2143], Khaw, Kay-Tee [0000-0002-8802-2903], Thompson, Deborah [0000-0003-1465-5799], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Medical Oncology, Obstetrics & Gynecology, Pathology, Cell biology, Medicum, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, Clinicum, Department of Oncology, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, and [ 1 ] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA [ 2 ] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA [ 3 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England [ 4 ] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol Program, Tampa, FL 33612 USA [ 5 ] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway [ 6 ] IRCCS, IOV, Immunol & Mol Oncol Unit, I-20133 Padua, Italy [ 7 ] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA [ 8 ] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA [ 9 ] Univ Chicago, Dept Med & Human Genet, Chicago, IL 60637 USA [ 10 ] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00029, Finland [ 11 ] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA [ 12 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada [ 13 ] Univ Toronto, Dept Mol Genet, Toronto, ON M5B 1W8, Canada [ 14 ] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5B 1W8, Canada [ 15 ] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA [ 16 ] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany [ 17 ] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA [ 18 ] Karolinska Univ Hosp, Dept Oncol, SE-17176 Stockholm, Sweden [ 19 ] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy [ 20 ] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 21 ] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland [ 22 ] Inst Qual & Efficiency Hlth Care IQWiG, D-50670 Cologne, Germany [ 23 ] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Breast Ctr Franconia, Dept Gynecol & Obstet,Univ Hosp Erlangen, D-91054 Erlangen, Germany [ 24 ] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Human Canc Genet Program, Madrid 28029, Spain [ 25 ] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Genotyping Unit CeGen, Madrid 28029, Spain [ 26 ] Biomed Network Rare Dis CIBERER, Madrid 28029, Spain [ 27 ] NYU, Sch Med, NYU Womens Canc Program, New York, NY 10016 USA [ 28 ] Univ Helsinki, Dept Oncol, FI-00029 Helsinki, Finland [ 29 ] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland [ 30 ] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany [ 31 ] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark [ 32 ] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany [ 33 ] Univ Tubingen, D-72074 Tubingen, Germany [ 34 ] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany [ 35 ] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany [ 36 ] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany [ 37 ] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA [ 38 ] IdISSC, Hosp Clin San Carlos, Mol Oncol Lab, Madrid 28040, Spain [ 39 ] Univ Pisa, Dept Lab Med, Sect Genet Oncol, I-56126 Pisa, Italy [ 40 ] Univ Hosp Pisa, I-56126 Pisa, Italy [ 41 ] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany [ 42 ] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW 2145, Australia [ 43 ] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany [ 44 ] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA [ 45 ] Columbia Univ, Dept Pediat, New York, NY 10032 USA [ 46 ] Columbia Univ, Dept Med, New York, NY 10032 USA [ 47 ] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium [ 48 ] Univ Sheffield, Dept Oncol, Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England [ 49 ] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2HQ, S Yorkshire, England [ 50 ] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden [ 51 ] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA [ 52 ] Univ Lyon, CNRS, UMR5286, Ctr Rech Cancerol Lyon,INSERM,U1052, F-69373 Lyon, France [ 53 ] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands [ 54 ] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZC Leiden, Netherlands [ 55 ] Univ Hosp Vall dHebron, VHIO, Oncogenet Grp, Barcelona 08035, Spain [ 56 ] Univ Autonoma Barcelona, Barcelona 08035, Spain [ 57 ] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA [ 58 ] CRO Aviano Natl Canc Inst, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy [ 59 ] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA [ 60 ] Univ Pretoria, Dept Genet, ZA-0007 Pretoria, South Africa [ 61 ] Univ London London Sch Hyg & Trop Med, Dept Non Communicable Dis Epidemiol, Keppel St, London WC1E 7HT, England [ 62 ] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ G1V 4G2, Canada [ 63 ] Univ Laval, Quebec City, PQ G1V 4G2, Canada [ 64 ] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England [ 65 ] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton SO16 6YD, Hants, England [ 66 ] Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden [ 67 ] Univ Lund Hosp, Dept Clin Genet, SE-22185 Lund, Sweden [ 68 ] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany [ 69 ] Comprehens Canc Ctr EMN, D-91054 Erlangen, Germany [ 70 ] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 71 ] Harvard Univ, Sch Med, Boston, MA 02115 USA [ 72 ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA [ 73 ] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, D-20246 Hamburg, Germany [ 74 ] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany [ 75 ] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany [ 76 ] Lund Univ, Ctr Primary Hlth Care Res, SE-22100 Malmo, Sweden [ 77 ] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens 15310, Greece [ 78 ] McGill Univ, Program Canc Genet, Montreal, PQ H3A 0G4, Canada [ 79 ] Univ Philadelphia, Philadelphia, PA 19104 USA [ 80 ] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel [ 81 ] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA [ 82 ] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, UCLA Sch Med, Los Angeles, CA 90095 USA [ 83 ] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, UCLA Sch Publ Hlth, Los Angeles, CA 90095 USA [ 84 ] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA [ 85 ] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02215 USA [ 86 ] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA [ 87 ] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark [ 88 ] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3010, Australia [ 89 ] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66205 USA [ 90 ] McGill Univ, Dept Med, Montreal, PQ H3G 2M1, Canada [ 91 ] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H4A 3J1, Canada [ 92 ] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT 84132 USA [ 93 ] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid 28029, Spain [ 94 ] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA [ 95 ] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland [ 96 ] CESP Ctr Res Epidemiol & Populat Hlth, Inserm Natl Inst Hlth & Med Res, U1018, Environm Epidemiol Canc, F-70115 Villejuif, France [ 97 ] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England [ 98 ] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA [ 99 ] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany [ 100 ] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark [ 101 ] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4029, Australia [ 102 ] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland [ 103 ] City Hope Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA 91010 USA [ 104 ] Netherlands Canc Inst, Family Canc Clin, NL-1000 BE Amsterdam, Netherlands [ 105 ] Erasmus MC Canc Inst, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands [ 106 ] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands [ 107 ] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia [ 108 ] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA [ 109 ] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia [ 110 ] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA [ 111 ] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic 8006, Australia [ 112 ] Univ Melbourne, Dept Oncol, Melbourne, Vic 8006, Australia [ 113 ] State Res Inst, Ctr Innovat Med, LT-08661 Vilnius, Lithuania [ 114 ] Aarhus Univ Hosp, Dept Clin Genet, DK-8200 Aarhus N, Denmark [ 115 ] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA [ 116 ] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England [ 117 ] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA [ 118 ] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland [ 119 ] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland [ 120 ] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England [ 121 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada [ 122 ] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany [ 123 ] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland [ 124 ] Hong Kong Hereditary Breast Canc Family Registry, Canc Genet Ctr, Hong Kong Sanat & Hosp, Hong Kong, Hong Kong, Peoples R China [ 125 ] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China [ 126 ] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium [ 127 ] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona 08908, Spain [ 128 ] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90032 USA [ 129 ] Univ Canc Ctr, Canc Epidemiol Program, Honolulu, HI 96813 USA [ 130 ] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden [ 131 ] Mayo Clin, Hlth Sci Res, Scotsdale, AZ 85259 USA [ 132 ] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA [ 133 ] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore [ 134 ] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA [ 135 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA [ 136 ] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA [ 137 ] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA [ 138 ] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy [ 139 ] Tech Univ Munich, Dept Obstet & Gynaecol, D-81675 Munich, Germany [ 140 ] Roswell Pk Canc Inst, NRG Oncol Stat & Data Management Ctr, Buffalo, NY 14263 USA [ 141 ] Case Western Reserve Univ, Sch Med, Dept Genom & Genome Sci, Cleveland, OH 44106 USA [ 142 ] Univ Hlth Network, Lab Med Program, Toronto, ON M5B 1W8, Canada [ 143 ] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5B 1W8, Canada [ 144 ] Invitae Corp, San Francisco, CA 94107 USA [ 145 ] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA [ 146 ] Natl Inst Oncol, Dept Mol Genet, H-1122 Budapest, Hungary [ 147 ] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 148 ] Seoul Natl Univ, Coll Med, Dept Prevent Med & Biomed Sci, Seoul 110799, South Korea [ 149 ] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea [ 150 ] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3508 GA Utrecht, Netherlands [ 151 ] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London SW7 2AZ, England [ 152 ] Fdn Ist FIRC Oncol Mol, IFOM, I-20133 Milan, Italy [ 153 ] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA [ 154 ] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Dept Clin Chem, FI-90220 Oulu, Finland [ 155 ] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Dept Clin Chem, FI-90220 Oulu, Finland [ 156 ] Univ Oulu, NordLab Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol,Bioctr Oulu, FI-90220 Oulu, Finland [ 157 ] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy [ 158 ] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England [ 159 ] Karolinska Univ Hosp, Dept Clin Genet, SE-17176 Stockholm, Sweden [ 160 ] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, A-1090 Vienna, Austria [ 161 ] Clalit Natl Israeli Canc Control Ctr, IL-34362 Haifa, Israel [ 162 ] Carmel Hosp, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel [ 163 ] B Rappaport Fac Med, IL-34362 Haifa, Israel [ 164 ] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA [ 165 ] Int Agcy Res Canc, F-69008 Lyon, France [ 166 ] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1006 BE Amsterdam, Netherlands [ 167 ] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, E-18014 Granada, Spain [ 168 ] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain [ 169 ] Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USA [ 170 ] Kings Coll London, Guys Hosp, Div Canc Studies, Res Oncol, London SE1 9RT, England [ 171 ] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, D-50931 Cologne, Germany [ 172 ] Univ Hosp Cologne, Fac Med, CIO, D-50931 Cologne, Germany [ 173 ] Univ Cologne, CMMC, D-50931 Cologne, Germany [ 174 ] John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW 2305, Australia [ 175 ] Univ Kansas, Med Ctr, Dept Hematol & Oncol, Kansas City, KS 66205 USA [ 176 ] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1V 4G2, Canada [ 177 ] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France [ 178 ] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia [ 179 ] Hannover Med Sch, D-30625 Hannover, Germany [ 180 ] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, SE-58185 Linkoping, Sweden [ 181 ] Inst Curie, Dept Tumour Biol, F-75248 Paris, France [ 182 ] Univ Paris 05, Sorbonne Paris Cite, F-75248 Paris, France [ 183 ] NHGRI, NIH, Bethesda, MD 20892 USA [ 184 ] Portuguese Oncol Inst, Dept Genet, P-4200072 Oporto, Portugal [ 185 ] Univ Porto, Biomed Sci Inst ICBAS, P-4200072 Oporto, Portugal [ 186 ] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia [ 187 ] Univ Malaya, Med Ctr, Canc Res Inst, Fac Med, Kuala Lumpur 50603, Malaysia [ 188 ] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA [ 189 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark [ 190 ] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia [ 191 ] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA [ 192 ] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 ZC Leiden, Netherlands [ 193 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England [ 194 ] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England [ 195 ] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona 08908, Spain [ 196 ] Civ MP Arezzo Hosp, Canc Registry, I-97100 Asp Ragusa, Italy [ 197 ] Civ MP Arezzo Hosp, Histopathol Unit, I-97100 Asp Ragusa, Italy [ 198 ] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA [ 199 ] Inst Populat Based Canc Res, Canc Registry Norway, N-0304 Oslo, Norway [ 200 ] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Pathol, NL-3000 CA Rotterdam, Netherlands [ 201 ] Charite, Inst Human Genet, D-13353 Berlin, Germany [ 202 ] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA [ 203 ] Univ Hosp Ulm, D-89075 Ulm, Germany [ 204 ] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway [ 205 ] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki 2016, Finland [ 206 ] Stanford Univ, Sch Med, Dept Hlth Res Policy Epidemiol, Stanford, CA 94305 USA [ 207 ] Univ Hosp, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, B-3000 Leuven, Belgium [ 208 ] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA [ 209 ] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain [ 210 ] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA [ 211 ] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia [ 212 ] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA

Subjects
0301 basic medicine, Oncology, General Physics and Astronomy, Genome-wide association study, Cyclophilins, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Brjóstakrabbamein, Genotype, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, CONFER SUSCEPTIBILITY, skin and connective tissue diseases, Cancer, GENE-EXPRESSION, Genetics, RISK, tRNA Methyltransferases, Multidisciplinary, Genome, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Loci, BRCA1 Protein, Chromosome Mapping, COMMON VARIANTS, IDENTIFY, PANCREATIC-CANCER, 3. Good health, Multidisciplinary Sciences, Biological sciences, Receptors, Estrogen, Chromosomes, Human, Pair 2, Science & Technology - Other Topics, Female, NAF12, medicine.medical_specialty, Heterozygote, Science, 3122 Cancers, Locus (genetics), Breast Neoplasms, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Càncer de mama, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Pancreatic cancer, MD Multidisciplinary, medicine, Genetic predisposition, Journal Article, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, Cancer och onkologi, Science & Technology, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, General Chemistry, Arfgengi, medicine.disease, TRNA Methyltransferases, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, 030104 developmental biology, Cancer and Oncology, Expression quantitative trait loci, Mutation, TELOMERE LENGTH, 3111 Biomedicine, Gene expression, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Genome-Wide Association Study
Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P, B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This study made use of data generated by the Wellcome Trust Case Control consortium. Functional studies were supported by the Florida Breast Cancer Foundation. A full description of funding and acknowledgments is provided in Supplementary Note 1.

Published
2018
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4. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals

Author

Clarke, R., Bennett, D., Parish, S., Lewington, S., Skeaff, M., Eussen, S.J.P.M., Lewerin, C., Stott, D.J., Armitage, J., Hankey, G.J., Lonn, E., Spence, J.D., Galan, P., de Groot, L.C., Halsey, J., Dangour, A.D., Collins, R., B-Vitamin Treatment Trialists' Collaboration, the, Grodstein, F., Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England, Partenaires INRAE, Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England, Univ Otago, Dept Human Nutr, Dunedin, New Zealand, Maastricht Univ, Med Ctr, CAPHRI, Sch Publ Hlth & Primary Care,Dept Epidemiol, Maastricht, Netherlands, Univ Bergen, Pharmacol Sect, Bergen, Norway, Univ Bergen, Dept Publ Hlth & Primary Care, Bergen, Norway, Univ Gothenburg, Sahlgrenska Acad, Inst Med, Sect Hematol & Coagulat,Dept Internal Med, Gothenburg, Sweden, Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland, Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia, McMaster Univ, Dept Med, Hamilton, ON, Canada, McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada, Univ Western Ontario, Dept Neurol, London, ON, Canada, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Wageningen Univ, Div Human Nutr & Epidemiol, NL-6700 AP Wageningen, Netherlands, London Sch Hyg & Trop Med, Dept Nutr & Publ Hlth Intervent Res, London WC1, England, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA, Epidemiologie, RS: CAPHRI School for Public Health and Primary Care, and RS: CAPHRI - Nutritional and Molecular Epidemiology

Subjects
Gerontology, Aging, Homocysteine, [SDV]Life Sciences [q-bio], Placebo-controlled study, Medicine (miscellaneous), cardiovascular-disease, PLACEBO-CONTROLLED TRIAL, law.invention, chemistry.chemical_compound, DOUBLE-BLIND, Cognition, 0302 clinical medicine, Randomized controlled trial, law, placebo-controlled trial, FOLIC-ACID SUPPLEMENTATION, 030212 general & internal medicine, older-adults, alzheimers-disease, Randomized Controlled Trials as Topic, Aged, 80 and over, Evidence-Based Medicine, Nutrition and Dietetics, medicine.diagnostic_test, VASCULAR-DISEASE, Middle Aged, RANDOMIZED CONTROLLED-TRIAL, folic-acid supplementation, ALZHEIMERS-DISEASE, CARDIOVASCULAR-DISEASE, Vitamin B Complex, randomized controlled-trial, stroke prevention, Alzheimer's disease, double-blind, Hyperhomocysteinemia, medicine.medical_specialty, vascular-disease, 03 medical and health sciences, Nutritional Epidemiology and Public Health, Internal medicine, medicine, Humans, Cognitive Dysfunction, OLDER-ADULTS, Aged, VLAG, Global Nutrition, Wereldvoeding, FOLIC-ACSUPPLEMENTATION, Mini–Mental State Examination, business.industry, STROKE PREVENTION, medicine.disease, B vitamins, chemistry, PLASMA HOMOCYSTEINE, Dietary Supplements, business, plasma homocysteine, 030217 neurology & neurosurgery
Abstract

Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain.\ud \ud Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging.\ud \ud Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)–type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals).\ud \ud Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: −0.054 ± 0.004 and −0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: −0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: −0.01; 95% CI: −0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: −0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment.\ud \ud Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.

Published
2016
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5. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Author

Jirong Long, Simon S. Cross, Marc Tischkowitz, Beth Y. Karlan, Trinidad Caldés, Fergus J. Couch, Charlotte Sagne, Ute Hamann, Olga M. Sinilnikova, Maria Kabisch, Richard C Sallari, Gad Rennert, Daniel Barrowdale, Elinor J. Sawyer, Anthony J. Swerdlow, Jenny Lester, Åke Borg, Anders Bojesen, Rosa B. Barkardottir, Simon A. Gayther, Heli Nevanlinna, Judy Garber, Norbert Arnold, Vilde Drageset Haakensen, Vessela N. Kristensen, Christopher G. Scott, Daehee Kang, Gillian Mitchell, Eitan Friedman, Laura Ottini, Diether Lambrechts, Manjeet K. Bolla, Robert L. Nussbaum, Tomasz Huzarski, Dieter Niederacher, Angela Cox, Rachel Laframboise, Maartje J. Hooning, Volker Arndt, Penny Soucy, Marjanka K. Schmidt, William Blot, Soo Hwang Teo, Anne Lise Børresen-Dale, Maria A. Caligo, Ana Osorio, Orland Diez, Gertraud Maskarinec, Johanna Rantala, Kelly-Anne Phillips, Pascal Guénel, Hidemi Ito, Miquel Angel Pujana, Anna H. Wu, Christy G. Woolcott, Maya Ghoussaini, Hatef Darabi, Sander Canisius, Kay-Tee Khaw, Irene Konstantopoulou, Carl Blomqvist, Christine Rappaport, Joan Brunet, Hermann Brenner, Sylvie Mazoyer, Irene L. Andrulis, Nicholas A Sinnott-Armstrong, Javier Benitez, Claudine Isaacs, Mahdi Moradi Marjaneh, Joseph Vijai, Jennifer Stone, Qin Wang, Caroline Seynaeve, Patricia A. Ganz, Sara Margolin, Paolo Radice, Janet E. Olson, Soo-Chin Lee, Mark H. Greene, Laura Papi, Carmel Apicella, Ava Kwong, Mitul Shah, Matthias W. Beckmann, Yael Laitman, Hoda Anton-Culver, Ans M.W. van den Ouweland, Sue K. Park, Annegien Broeks, Georgia Chenevix-Trench, Jonathan Beesley, Nadja Bogdanova-Markov, Paolo Peterlongo, Paraskevi Apostolou, Bernardo Bonanni, Frederik Marmé, Veli-Matti Kosma, Alfons Meindl, Brian E. Henderson, Rulla M. Tamimi, Siranoush Manoukian, Bent Ejlertsen, Miroslav Kapuscinski, Juliet D. French, Mark E. Sherman, Ji Yeob Choi, Graham G. Giles, Stacey L. Edwards, Evgeny N. Imyanitov, Kamila Czene, Thomas Hansen, Nick Orr, Susanne Kaufmann, Lenka Foretova, Celine M. Vachon, Edith Olah, Anja Rudolph, Arto Mannermaa, Phuong L. Mai, Isabel dos-Santos-Silva, Haran Sivakumaran, Francesca Damiola, Christian F. Singer, Muhammad Usman Rashid, Ed Dicks, Mikael Hartman, Antonis C. Antoniou, Dominique Stoppa-Lyonnet, Douglas F. Easton, Alison M. Dunning, John L. Hopper, Nadine Tung, Annika Lindblom, Kristiina Aittomäki, Kenneth Muir, Sue Healey, Cheng Har Yip, Mads Thomassen, Melissa C. Southey, Ramunas Janavicius, Cecilia M. Dorfling, Christine B. Ambrosone, Siddhartha Kar, Mary B. Daly, Artitaya Lophatananon, Rachel Rando, Banu Arun, Christopher A. Haiman, Catherine M. Phelan, Margaret Hills, Manuel R. Teixeira, Diana Torres, Hans Wildiers, Andrew K. Godwin, Keith Humphreys, Katri Pylkäs, Monika Jarosz, Susan L. Neuhausen, Montserrat Garcia-Closas, Robert Winqvist, Joe Dennis, Sook-Yee Yoon, Wei Zheng, Mitch Dowsett, Gord Glendon, Natasha Bogdanova, Suleeporn Sangrajrang, Steve Ellis, Paul Brennan, Lee Eunjung, Keitaro Matsuo, Jacek Gronwald, David E. Goldgar, Debra Frost, Chiu-Chen Tseng, Henrik Flyger, Kristine M. Hillman, Susan M. Domchek, Elena Lopez-Knowles, Bernard Peissel, Anna von Wachenfeldt, Karoline Kuchenbaecker, Anna Jakubowska, Paul D.P. Pharoah, Jose Ignacio Arias Perez, Kim De Leeneer, Roger L. Milne, Peter A. Fasching, Louise Izatt, Saundra S. Buys, Lesley McGuffog, Elizabeth J. van Rensburg, Pei-Ei Wu, Peter Devilee, Åslaug Helland, Qiuyin Cai, Peter J. Hulick, Miguel de la Hoya, Esther M. John, Kerstin Rhiem, Jan Lubinski, Karen A. Pooley, Marion Piedmonte, Catherine S. Healey, Mark S. Goldberg, Xiao-Ou Shu, Antoinette Hollestelle, Mary Beth Terry, Jenny Chang-Claude, Silje Nord, Chen-Yang Shen, Hiltrud Brauch, Kathleen Claes, Jason Sang Hun Lee, Sofia Khan, Katherine L. Nathanson, Hans Ehrencrona, Olufunmilayo I. Olopade, Stig E. Bojesen, Matti A. Rookus, Andrew Lee, Rita K. Schmutzler, Julian Peto, Jeffrey N. Weitzel, Barbara Burwinkel, Arjen R. Mensenkamp, Jacques Simard, Yu-Tang Gao, Robert Luben, S. Drury, Thilo Dörk, Laima Tihomirova, Per Hall, Barbara Perkins, Simona Agata, Jonine D. Figueroa, Julia A. Knight, Kenneth Offit, Kyriaki Michailidou, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Noralane M. Lindor, Deborah J. Thompson, Marco Montagna, Clinical Genetics, Medical Oncology, Obstetrics & Gynecology, Dunning, Alison [0000-0001-6651-7166], Thompson, Deborah [0000-0003-1465-5799], Pooley, Karen [0000-0002-1274-9460], Dicks, Ed [0000-0002-0617-0401], Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Ghoussaini, Maya [0000-0002-2415-2143], Lee, Andrew [0000-0003-0677-0252], Tischkowitz, Marc [0000-0002-7880-0628], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and [ 1 ] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England [ 2 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England [ 3 ] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia [ 4 ] Breakthrough Breast Canc Res Ctr, Breast Canc Res, London, England [ 5 ] Royal Marsden Hosp, Acad Biochem, London SW3 6JJ, England [ 6 ] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA [ 7 ] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA [ 8 ] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands [ 9 ] Univ Melbourne, Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia [ 10 ] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia [ 11 ] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England [ 12 ] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England [ 13 ] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen Nuremberg Metropolit, D-91054 Erlangen, Germany [ 14 ] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA [ 15 ] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England [ 16 ] Kings Coll London, Guys Hosp, Div Canc Studies, Res Oncol, London, England [ 17 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England [ 18 ] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England [ 19 ] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany [ 20 ] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany [ 21 ] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany [ 22 ] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany [ 23 ] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France [ 24 ] Univ Paris Sud, Villejuif, France [ 25 ] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark [ 26 ] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark [ 27 ] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark [ 28 ] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark [ 29 ] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Madrid, Spain [ 30 ] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain [ 31 ] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA [ 32 ] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA [ 33 ] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany [ 34 ] German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany [ 35 ] Tech Univ Munich, Dept Obstet & Gynaecol, D-80290 Munich, Germany [ 36 ] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany [ 37 ] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [ 38 ] Univ Hosp, Ctr Integrated Oncol, Cologne, Germany [ 39 ] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany [ 40 ] Univ Tubingen, Tubingen, Germany [ 41 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany [ 42 ] Helsinki Univ Cent Hosp, Dept Clin Genet, Helsinki, Finland [ 43 ] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Oncol, Helsinki, Finland [ 44 ] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Aichi, Japan [ 45 ] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan [ 46 ] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany [ 47 ] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany [ 48 ] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden [ 49 ] Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden [ 50 ] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland [ 51 ] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland [ 52 ] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland [ 53 ] Vesalius Res Ctr, Leuven, Belgium [ 54 ] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium [ 55 ] Univ Hosp Leuven, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, Leuven, Belgium [ 56 ] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany [ 57 ] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany [ 58 ] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy [ 59 ] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Basis Genet Risk & Genet Testing, Milan, Italy [ 60 ] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA [ 61 ] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia [ 62 ] McGill Univ, Dept Med, Montreal, PQ, Canada [ 63 ] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada [ 64 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia [ 65 ] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia [ 66 ] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway [ 67 ] Univ Oslo, Inst Clin Med, Oslo, Norway [ 68 ] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway [ 69 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA [ 70 ] Univ Oulu, NordLab Oulu Univ Hosp, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 71 ] Univ Oulu, NordLab Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland [ 72 ] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 73 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada [ 74 ] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada [ 75 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada [ 76 ] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada [ 77 ] Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands [ 78 ] Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands [ 79 ] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands [ 80 ] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA [ 81 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 82 ] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands [ 83 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 84 ] Univ Sheffield, Sheffield Canc Res, Dept Oncol, Sheffield, S Yorkshire, England [ 85 ] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England [ 86 ] Int Epidemiol Inst, Rockville, MD USA [ 87 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea [ 88 ] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea [ 89 ] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea [ 90 ] Natl Univ Hlth Syst, Dept Haematol Oncol, Singapore, Singapore [ 91 ] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore [ 92 ] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore [ 93 ] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore [ 94 ] Pontificia Univ Javerianar, Inst Human Genet, Bogota, Colombia [ 95 ] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland [ 96 ] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France [ 97 ] Natl Canc Inst, Bangkok, Thailand [ 98 ] Roswell Pk Canc Inst, Buffalo, NY 14263 USA [ 99 ] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA [ 100 ] China Med Univ, Sch Publ Hlth, Taichung, Taiwan [ 101 ] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei, Taiwan [ 102 ] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England [ 103 ] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England [ 104 ] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England [ 105 ] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia [ 106 ] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA [ 107 ] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA [ 108 ] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA [ 109 ] Univ Utah, Sch Med, Dept Dermatol, Huntsman Canc Inst, Salt Lake City, UT USA [ 110 ] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA [ 111 ] State Res Inst Ctr Innovat Med, Vilnius, Lithuania [ 112 ] Latvian Biomed Res & Study Ctr, Riga, Latvia [ 113 ] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA [ 114 ] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa [ 115 ] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA [ 116 ] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark [ 117 ] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark [ 118 ] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain [ 119 ] Biomed Network Rare Dis CIBERER, Madrid, Spain [ 120 ] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain [ 121 ] City Hope Clin Canc Genom Community Res Network, Duarte, CA USA [ 122 ] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA [ 123 ] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy [ 124 ] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, Via Venezian 1, I-20133 Milan, Italy [ 125 ] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy [ 126 ] Univ Roma La Sapienza, Dept Mol Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy [ 127 ] Aghia Paraskevi Attikis, Natl Ctr Sci Res Demokritos, INRASTES Inst Nucl & Radiol Sci & Technol, Mol Diagnost Lab, Athens, Greece [ 128 ] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA [ 129 ] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan [ 130 ] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Clin Genet, London, England [ 131 ] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA [ 132 ] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany [ 133 ] Univ Dusseldorf, Dusseldorf, Germany [ 134 ] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [ 135 ] Univ Hosp Cologne, Ctr Mol Med Cologne, Ctr Integrated Oncol, Cologne, Germany [ 136 ] Univ Munster, Inst Human Genet, D-48149 Munster, Germany [ 137 ] Univ Lyon 1, CNRS UMR 5286, INSERM U1052, Ctr Rech Cancerol Lyon, F-69365 Lyon, France [ 138 ] Inst Curie, Dept Tumour Biol, Paris, France [ 139 ] Univ Paris 05, Sorbonne Paris Cite, Paris, France [ 140 ] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France [ 141 ] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA [ 142 ] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium [ 143 ] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, Madrid, Spain [ 144 ] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland [ 145 ] Univ Helsinki, Cent Hosp, Helsinki, Finland [ 146 ] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands [ 147 ] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands [ 148 ] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands [ 149 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China [ 150 ] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China [ 151 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary [ 152 ] Vall dHebron Univ Hosp, VHIO, Oncogenet Lab, Barcelona, Spain [ 153 ] Catalan Inst Oncol, IDIBGI, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain [ 154 ] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Breast Canc & Syst Biol Unit, Barcelona, Spain [ 155 ] Univ Iceland, Fac Med, Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital University of Iceland [ 156 ] Univ Iceland, Fac Med, Biomed Ctr BMC, Reykjavik, Iceland [ 157 ] Ctr Hosp Univ Quebec, Div Med Genet, Quebec City, PQ, Canada [ 158 ] Univ Laval, Quebec City, PQ, Canada [ 159 ] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada [ 160 ] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy [ 161 ] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal [ 162 ] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal [ 163 ] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA [ 164 ] McGill Univ, Program Canc Genet, Montreal, PQ, Canada [ 165 ] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic [ 166 ] Masaryk Univ, Fac Med, Brno, Czech Republic [ 167 ] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA [ 168 ] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria [ 169 ] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA [ 170 ] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, US NIH, Rockville, MD USA [ 171 ] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel [ 172 ] Technion Israel Inst Technol, Bruce Rappaport Fac Med, POB 9649, IL-31096 Haifa, Israel [ 173 ] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel [ 174 ] NN Petrov Oncol Res Inst, St Petersburg, Russia [ 175 ] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA [ 176 ] Peter MacCallum Canc Ctr, Div Canc Med, East Melbourne, Vic, Australia [ 177 ] Roswell Pk Canc Inst, Stat & Data Management Ctr, NRG Oncol, Buffalo, NY 14263 USA [ 178 ] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada [ 179 ] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada [ 180 ] Vejle Hosp, Dept Clin Genet, Vejle, Denmark [ 181 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark [ 182 ] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy [ 183 ] Univ Hosp Pisa, Pisa, Italy [ 184 ] Univ Malaya, Univ Malaya Med Ctr, Fac Med, Univ Malaya Canc Res Inst, Kuala Lumpur, Malaysia [ 185 ] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel [ 186 ] Lund Univ, Dept Oncol, Lund, Sweden [ 187 ] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden [ 188 ] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden [ 189 ] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden [ 190 ] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 191 ] Univ Calif Los Angeles, Sch Med, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA [ 192 ] Univ Calif Los Angeles, Sch Publ Hlth, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA [ 193 ] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA [ 194 ] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA [ 195 ] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA [ 196 ] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia [ 197 ] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia [ 198 ] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA [ 199 ] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA [ 200 ] Dalhousie Univ, Dept Obstet Gynaecol & Pediat, Halifax, NS, Canada [ 201 ] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia [ 202 ] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 203 ] Harvard Univ, Sch Med, Boston, MA USA [ 204 ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA [ 205 ] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA [ 206 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England

Subjects
0301 basic medicine, Genes, BRCA2, Estrogen receptor, MODIFIERS, Gene Expression, Genome-wide association study, Cell Cycle Proteins, DISEASE, Breast cancer, Risk Factors, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], SUSCEPTIBILITY LOCUS, MAMMOGRAPHIC DENSITY, Regulation of gene expression, Genetics, Research Support, Non-U.S. Gov't, Estrogen Receptor alpha/genetics, Phenotype, 3. Good health, Gene Expression Regulation, Neoplastic, Medical genetics, Chromosomes, Human, Pair 6, Female, BONE-MINERAL DENSITY, NAF12, Protein Binding, EXPRESSION, medicine.medical_specialty, Locus (genetics), Breast Neoplasms, Estrògens, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, Article, Càncer de mama, 03 medical and health sciences, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, REVEALS, medicine, Journal Article, cancer, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, breast, Genetic Association Studies, Base Sequence, Estrogen Receptor alpha, Genetic Variation, Arfgengi, medicine.disease, Estrogen, 030104 developmental biology, breast cancer, BRCA1, BRCA2, Carrier Proteins, Estrogen receptor alpha, Research Support, U.S. Gov't, Non-P.H.S, Meta-Analysis
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. National Institute for Health Research (NIHR) info:eu-repo/grantAgreement/EC/FP7/223175 Cancer Research UK C1287/A10118 C1287/A10710 C12292/A11174 C1281/A12014 C5047/A8384 C5047/A15007 C5047/A10692 C8197/A16565 US National Institutes of Health (NIH) CA128978 CA192393 CA116167 CA176785 US National Institutes of Health (NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer) CA116201 Post-Cancer GWAS initiative 1U19 CA148537 1U19 CA148065 1U19 CA148112 Post-Cancer GWAS initiative (GAME-ON initiative) US Department of Defense W81XWH-10-1-0341 Canadian Institutes of Health Research (CIHR) Komen Foundation for the Cure Breast Cancer Research Foundation Ovarian Cancer Research Fund

Published
2016
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6. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels

Author

Michael Sgro, Finn Ebbesen, Vinod K. Bhutani, Simon Cousens, Tina M. Slusher, Rintaro Mori, Lizhong Du, Joy E Lawn, A. A. Okolo, Bolajoko O. Olusanya, Hannah Blencowe, Vinod K. Paul, Jennifer J. Bell, Rajesh Khanna, Alvin Zipursky, Maria Fernanda Branco de Almeida, Praveen Kumar, Nahed Fahmy, Hosp Sick Children, Stanford Univ, London Sch Hyg & Trop Med, Saving Newborn Lives Save Children, St Michaels Hosp, Aalborg Univ Hosp, Natl Ctr Child Hlth & Dev, Univ Minnesota, Kasr Al Aini Univ, All India Inst Med Sci, Zhejiang Univ, Nigerian Soc Neonatal Med, Universidade Federal de São Paulo (UNIFESP), Ctr Hlth Start Initiat, and Post Grad Inst Med Educ & Res

Subjects
Population Study, Pediatrics, medicine.medical_specialty, Models, Statistical, South asia, Neonatal mortality, business.industry, Incidence, Incidence (epidemiology), Infant, Newborn, Gestational age, Disease, Global Health, Rh Isoimmunization, medicine.disease, History, 21st Century, Erythroblastosis, Fetal, Meta-analysis, Pediatrics, Perinatology and Child Health, medicine, Humans, Kernicterus, Hyperbilirubinemia, Neonatal, Neonatal death, business
Abstract

March of Dimes Prematurity Research Center at Stanford University School of Medicine Bill and Melinda Gates Foundation BACKGROUND: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.METHODS: Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.RESULTS: Twenty-four million (18% of 134 million live births >= 32wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. of these, 480,700(0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.CONCLUSION: Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries. Hosp Sick Children, Programme Global Paediat Res, Toronto, ON M5G 1X8, Canada Stanford Univ, Dept Pediat, Div Neonatal & Dev Med, Sch Med,Lucile Packard Childrens Hosp, Stanford, CA 94305 USA London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England Saving Newborn Lives Save Children, New Delhi, India St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada St Michaels Hosp, Dept Paediat, Toronto, ON M5B 1W8, Canada Aalborg Univ Hosp, Dept Pediat, Aalborg, Denmark Natl Ctr Child Hlth & Dev, Dept Hlth Policy, Tokyo, Japan Univ Minnesota, Ctr Global Pediat, Minneapolis, MN USA Kasr Al Aini Univ, El Mounira Childrens Hosp, Dept Pediat, Cairo, Egypt All India Inst Med Sci, WHO Collaborating Ctr Training & Res Newborn Care, New Delhi, India Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China Nigerian Soc Neonatal Med, Lagos, Nigeria Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil Ctr Hlth Start Initiat, Lagos, Nigeria Post Grad Inst Med Educ & Res, Chandigarh, India London Sch Hyg & Trop Med, Ctr Maternal Reprod & Child Hlth, London WC1, England Saving Newborn Lives Save Children, Washington, DC USA Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil Web of Science

Published
2013
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7. The variability and predictors of quality of AIDS care services in Brazil

Author

Regina Melchior, Maria Teresa Seabra Soares de Britto e Alves, Elen Rose Lodeiro Castanheira, Cáritas Relva Basso, Shaun Conway, Maria Ines Battistella Nemes, Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), London Sch Hyg & Trop Med, and Universidade Estadual de Londrina (UEL)

Subjects
Quality management, Service delivery framework, media_common.quotation_subject, HIV Infections, Ambulatory Care Facilities, Ambulatory care, Acquired immunodeficiency syndrome (AIDS), Surveys and Questionnaires, Environmental health, Health care, medicine, Cluster Analysis, Humans, Quality (business), Quality of Health Care, media_common, Service (business), Acquired Immunodeficiency Syndrome, Service quality, business.industry, lcsh:Public aspects of medicine, Health Policy, Administrative Personnel, lcsh:RA1-1270, medicine.disease, Benchmarking, Logistic Models, Anti-Retroviral Agents, Health Care Surveys, Medical emergency, business, Research Article
Abstract

Made available in DSpace on 2013-08-28T14:11:14Z (GMT). No. of bitstreams: 1 WOS000265765700001.pdf: 537714 bytes, checksum: 44c99c3390c029dd72043e36193dd987 (MD5) Made available in DSpace on 2013-09-30T18:24:04Z (GMT). No. of bitstreams: 2 WOS000265765700001.pdf: 537714 bytes, checksum: 44c99c3390c029dd72043e36193dd987 (MD5) WOS000265765700001.pdf.txt: 39431 bytes, checksum: 44be86bc41726383d198f5877fb0be57 (MD5) Previous issue date: 2009-03-20 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:38:25Z No. of bitstreams: 2 WOS000265765700001.pdf: 537714 bytes, checksum: 44c99c3390c029dd72043e36193dd987 (MD5) WOS000265765700001.pdf.txt: 39431 bytes, checksum: 44be86bc41726383d198f5877fb0be57 (MD5) Made available in DSpace on 2014-05-20T13:38:25Z (GMT). No. of bitstreams: 2 WOS000265765700001.pdf: 537714 bytes, checksum: 44c99c3390c029dd72043e36193dd987 (MD5) WOS000265765700001.pdf.txt: 39431 bytes, checksum: 44be86bc41726383d198f5877fb0be57 (MD5) Previous issue date: 2009-03-20 Background: Since establishing universal free access to antiretroviral therapy in 1996, the Brazilian Health System has increased the number of centers providing HIV/AIDS outpatient care from 33 to 540. There had been no formal monitoring of the quality of these services until a survey of 336 AIDS health centers across 7 Brazilian states was undertaken in 2002. Managers of the services were asked to assess their clinics according to parameters of service inputs and service delivery processes. This report analyzes the survey results and identifies predictors of the overall quality of service delivery.Methods: The survey involved completion of a multiple-choice questionnaire comprising 107 parameters of service inputs and processes of delivering care, with responses assessed according to their likely impact on service quality using a 3-point scale. K-means clustering was used to group these services according to their scored responses. Logistic regression analysis was performed to identify predictors of high service quality.Results: The questionnaire was completed by 95.8% (322) of the managers of the sites surveyed. Most sites scored about 50% of the benchmark expectation. K-means clustering analysis identified four quality levels within which services could be grouped: 76 services (24%) were classed as level 1 (best), 53 (16%) as level 2 (medium), 113 (35%) as level 3 (poor), and 80 (25%) as level 4 (very poor). Parameters of service delivery processes were more important than those relating to service inputs for determining the quality classification. Predictors of quality services included larger care sites, specialization for HIV/AIDS, and location within large municipalities.Conclusion: The survey demonstrated highly variable levels of HIV/AIDS service quality across the sites. Many sites were found to have deficiencies in the processes of service delivery processes that could benefit from quality improvement initiatives. These findings could have implications for how HIV/AIDS services are planned in Brazil to achieve quality standards, such as for where service sites should be located, their size and staffing requirements. A set of service delivery indicators has been identified that could be used for routine monitoring of HIV/AIDS service delivery for HIV/AIDS in Brazil (and potentially in other similar settings). São Paulo State Univ, UNESP, Fac Med Botucatu, Dept Publ Hlth, São Paulo, Brazil Univ São Paulo, Fac Med, Dept Prevent Med, São Paulo, Brazil London Sch Hyg & Trop Med, Hlth Policy Unit, London WC1, England Univiversidade Estadual de Londrina (UEL), Dept Publ Hlth, Maringa, Parana, Brazil São Paulo State Univ, UNESP, Fac Med Botucatu, Dept Publ Hlth, São Paulo, Brazil

Published
2009

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