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54. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

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Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael

Subjects
Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Published
2018

61. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, Zychlinsky, A, Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, and Zychlinsky, A

Abstract

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Published
2019

62. Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study

Author

Manchanda, R, Burnell, M, Gaba, F, Sanderson, S, Loggenberg, K, Gessler, S, Wardle, J, Side, L, Desai, R, Brady, AF, Dorkins, H, Wallis, Y, Chapman, C, Jacobs, C, Tomlinson, I, Beller, U, Menon, U, Jacobs, I, Manchanda, R, Burnell, M, Gaba, F, Sanderson, S, Loggenberg, K, Gessler, S, Wardle, J, Side, L, Desai, R, Brady, AF, Dorkins, H, Wallis, Y, Chapman, C, Jacobs, C, Tomlinson, I, Beller, U, Menon, U, and Jacobs, I

Abstract

© 2019 Royal College of Obstetricians and Gynaecologists Objective: To evaluate factors affecting unselected population-based BRCA testing in Ashkenazi Jews (AJ). Design: Cohort-study set within recruitment to the GCaPPS trial (ISRCTN73338115). Setting: North London AJ population. Population or sample: Ashkenazi Jews women/men >18 years, recruited through self-referral. Methods: Ashkenazi Jews women/men underwent pre-test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio-demographic/family history/knowledge/psychological well-being along with benefits/risks/cultural influences (18-item questionnaire measuring ‘attitude’). Four-item Likert-scales analysed initial ‘interest’ and ‘intention-to-test’ pre-counselling. Uni- and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item-Response Theory and graded-response models modelled responses to 18-item questionnaire. Main outcome measures: Interest, intention, uptake, attitude towards BRCA testing. Results: A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre-test genetic-counselling. During the pre-counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA-related knowledge (P = 0.013) and degree-level education (P = 0.01) were positively and negatively (respectively) associated with intention-to-test. Being married/cohabiting had four-fold higher odds for BRCA testing uptake (P = 0.009). Perceived benefits were associated with higher pre-counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision-making.

Published
2019

69. PREDICTING RISK OF OVARIAN MALIGNANCY IMPROVED SCREENING AND EARLY DETECTION FEASIBILITY STUDY (PROMISE-FS)

Author

Manchanda, R, Gaba, F, Bottla, K, Mousa, K, Burnell, M, Kalsi, J, Gentry-Maharaj, A, Antoniou, A, Blyuss, O, Zaikin, A, Lee, A, Lanceley, A, Sanderson, S, Waller, J, Gayther, S, Ramus, S, Wallis, Y, Skates, S, Menon, U, and Jacobs, I

Abstract

To evaluate feasibility of undertaking a study to stratify a general population on the basis of their predicted ovarian cancer (OC) risk and offer risk management options of screening and prevention

Published
2018
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70. Randomised trial of unselected BRCA testing in ashkenazi jews: long term outcomes and factors affecting uptake of testing

Author

Manchanda, R, primary, Burnell, M, additional, Gaba, F, additional, Desai, R, additional, Wardle, J, additional, Gessler, S, additional, Side, L, additional, Sanderson, S, additional, Loggenberg, K, additional, Brady, A, additional, Dorkins, H, additional, Wallis, Y, additional, Chapman, C, additional, Jacobs, C, additional, Legood, R, additional, Beller, U, additional, Tomlinson, I, additional, Menon, U, additional, and Jacobs, I, additional

Published
2019
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71. Randomised trial of population‐based BRCA testing in Ashkenazi Jews: long‐term outcomes

Author

Manchanda, R, primary, Burnell, M, additional, Gaba, F, additional, Desai, R, additional, Wardle, J, additional, Gessler, S, additional, Side, L, additional, Sanderson, S, additional, Loggenberg, K, additional, Brady, AF, additional, Dorkins, H, additional, Wallis, Y, additional, Chapman, C, additional, Jacobs, C, additional, Legood, R, additional, Beller, U, additional, Tomlinson, I, additional, Menon, U, additional, and Jacobs, I, additional

Published
2019
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72. 81 Attitude towards and factors affecting uptake of population based BRCA testing in ashkenazi jews: a cohort study

Author

Manchanda, R, primary, Burnell, M, additional, Gaba, F, additional, Sanderson, S, additional, Loggenberg, K, additional, Gessler, S, additional, Wardle, J, additional, Side, L, additional, Desai, R, additional, Brady, A, additional, Dorkins, H, additional, Wallis, Y, additional, Chapman, C, additional, Jacobs, C, additional, Tomlinson, I, additional, Beller, U, additional, Menon, U, additional, and Jacobs, I, additional

Published
2019
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75. Attitude towards and factors affecting uptake of population‐basedBRCAtesting in the Ashkenazi Jewish population: a cohort study

Author

Manchanda, R, primary, Burnell, M, additional, Gaba, F, additional, Sanderson, S, additional, Loggenberg, K, additional, Gessler, S, additional, Wardle, J, additional, Side, L, additional, Desai, R, additional, Brady, AF, additional, Dorkins, H, additional, Wallis, Y, additional, Chapman, C, additional, Jacobs, C, additional, Tomlinson, I, additional, Beller, U, additional, Menon, U, additional, and Jacobs, I, additional

Published
2019
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78. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Author

Bowman, P, Sulen, A, Barbetti, F, Beltrand, J, Svalastoga, P, Codner, E, Tessmann, EH, Juliusson, PB, Skrivarhaug, T, Pearson, ER, Flanagan, SE, Babiker, T, Thomas, NJ, Shepherd, MH, Ellard, S, Klimes, I, Szopa, M, Polak, M, Iafusco, D, Hattersley, AT, Njolstad, PR, Houghton, J, Patel, KA, Mathews, F, De Franco, E, Ford, T, Pillai, JK, Finn, R, Chakera, A, Iotova, V, Malecki, MT, Klupa, T, Gasperikova, D, Stanik, J, Barak, L, Dankovcikova, A, Palko, M, Walker, J, Visser, U, Howard, N, Lafferty, T, Cummings, E, Guntamukkala, P, Rose, D, Hughes, N, Couch, B, Punthakee, Z, Van der Meulen, J, LeGault, L, Sanderson, S, Krishnaswamy, R, Ho, J, Modgil, G, Lambert, P, Shield, JPH, Hoddinott, R, Burrows, A, Chetan, R, Hakeem, V, Werner, A, Muther, S, Deiss, D, Raile, K, Weisner, T, Kapellen, T, Akkurt, I, Menzel, U, Klinge, A, Schmidt, D, Heffernan, E, Carson, D, Uehara, A, Hasegawa, S, Kuulasmaa, H, Tuomi, T, Vermeulen, G, Mul, D, Jaap, A, Hill, D, Hunter, I, Rincon, M, McVie, R, Williams, T, Saxena, V, Al-Abdullah, A, Tinklin, T, Kaufman, E, Davis, L, O'Riordan, S, O'Connell, SM, Holl, R, Schebek, M, De Gallen, B, Voorhoeve, P, Malievsky, O, Mathew, R, Abdul-Latif, H, Aisenberg, J, Ioacara, S, Cameron, FJ, Sanchez, J, Jones, K, Van der Velde, R, Van den Bergh, J, Woodhead, H, Tjora, E, Irgens, H, Hogåsen, AK, Odegard, R, Hathout, EH, Nuboer, R, Pruhova, S, Shehadeh, N, Silva, JMCL, Cave, H, Fauret, A-L, Hoarau, M, Coutant, R, Metz, C, Bertrand, A-M, Bruel, H, Cartigny, M, Weill, J, Bizzarri, C, Bonfanti, R, Cadario, F, Cauvin, V, Chiari, G, Delvecchio, M, Piccinno, E, Faleschini, E, Pesavento, R, Rabbone, I, Tumini, S, Bowman, P, Sulen, A, Barbetti, F, Beltrand, J, Svalastoga, P, Codner, E, Tessmann, EH, Juliusson, PB, Skrivarhaug, T, Pearson, ER, Flanagan, SE, Babiker, T, Thomas, NJ, Shepherd, MH, Ellard, S, Klimes, I, Szopa, M, Polak, M, Iafusco, D, Hattersley, AT, Njolstad, PR, Houghton, J, Patel, KA, Mathews, F, De Franco, E, Ford, T, Pillai, JK, Finn, R, Chakera, A, Iotova, V, Malecki, MT, Klupa, T, Gasperikova, D, Stanik, J, Barak, L, Dankovcikova, A, Palko, M, Walker, J, Visser, U, Howard, N, Lafferty, T, Cummings, E, Guntamukkala, P, Rose, D, Hughes, N, Couch, B, Punthakee, Z, Van der Meulen, J, LeGault, L, Sanderson, S, Krishnaswamy, R, Ho, J, Modgil, G, Lambert, P, Shield, JPH, Hoddinott, R, Burrows, A, Chetan, R, Hakeem, V, Werner, A, Muther, S, Deiss, D, Raile, K, Weisner, T, Kapellen, T, Akkurt, I, Menzel, U, Klinge, A, Schmidt, D, Heffernan, E, Carson, D, Uehara, A, Hasegawa, S, Kuulasmaa, H, Tuomi, T, Vermeulen, G, Mul, D, Jaap, A, Hill, D, Hunter, I, Rincon, M, McVie, R, Williams, T, Saxena, V, Al-Abdullah, A, Tinklin, T, Kaufman, E, Davis, L, O'Riordan, S, O'Connell, SM, Holl, R, Schebek, M, De Gallen, B, Voorhoeve, P, Malievsky, O, Mathew, R, Abdul-Latif, H, Aisenberg, J, Ioacara, S, Cameron, FJ, Sanchez, J, Jones, K, Van der Velde, R, Van den Bergh, J, Woodhead, H, Tjora, E, Irgens, H, Hogåsen, AK, Odegard, R, Hathout, EH, Nuboer, R, Pruhova, S, Shehadeh, N, Silva, JMCL, Cave, H, Fauret, A-L, Hoarau, M, Coutant, R, Metz, C, Bertrand, A-M, Bruel, H, Cartigny, M, Weill, J, Bizzarri, C, Bonfanti, R, Cadario, F, Cauvin, V, Chiari, G, Delvecchio, M, Piccinno, E, Faleschini, E, Pesavento, R, Rabbone, I, and Tumini, S

Abstract

BACKGROUND: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. METHODS: In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. FINDINGS: 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3-10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at al

Published
2018

79. Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry

Author

Juvet, S, Moshkelgosha, S, Sanderson, S, Hester, J, Wood, K, and Bushell, A

Subjects
CD4-Positive T-Lymphocytes, Isoantigens, dendritic cell, T-Lymphocytes, General Chemical Engineering, Immunology, T-Lymphocytes, Regulatory, antigen-presenting cell, General Biochemistry, Genetics and Molecular Biology, Immune Tolerance, Animals, Transplantation, Homologous, Antigens, Immunosuppression Therapy, tolerance, General Immunology and Microbiology, allograft rejection, General Neuroscience, immune synapse, Graft Survival, T cell, Dendritic Cells, imaging flow cytometry, Flow Cytometry, Issue 122, Mice, Inbred CBA, Heart Transplantation, transplantation
Abstract

The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy. We recently made use of an imaging flow cytometry approach to define the proportion of recipient T cells capable of forming mature immune synapses with donor antigen-presenting cells (APCs). Using a well-characterized mouse heart transplant model, we have shown that the frequency of in vitro immune synapses among T-APC membrane contact events strongly predicted allograft outcome in rejection, tolerance, and a situation where transplant survival depends on induced regulatory T cells. The frequency of T-APC contacts increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. The addition of regulatory T cells to the in vitro system reduced prolonged T-APC contacts. Critically, this effect was also seen with human polyclonally expanded, naturally occurring regulatory T cells, which are known to control the rejection of human tissues in humanized mouse models. Further development of this approach may allow for a deeper characterization of the alloreactive T-cell compartment in transplant recipients. In the future, further development and evaluation of this method using human cells may form the basis for assays used to select patients for immunosuppression minimization, and it can be used to measure the impact of tolerogenic therapies in the clinic.

Published
2017

80. Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Author

Nucci, A. M., Virtanen, S. M., Sorkio, S., Barlund, S., Cuthbertson, D., Uusitalo, U., Lawson, M. L., Salonen, M., Berseth, C. L., Ormisson, A., Lehtonen, E., Savilahti, E., Becker, D. J., Dupre, J., Krischer, J. P., Knip, M., Akerblom, H. K., Mandrup-Poulsen, T., Arjas, E., Laara, E., Lernmark, A., Schmidt, B., Hyytinen, M., Koski, K., Koski, M., Pajakkala, E., Shanker, L., Bradley, B., Dosch, H. -M., Fraser, W., Lawson, M., Mahon, J. L., Sermer, M., Taback, S. P., Becker, D., Franciscus, M., Nucci, A., Palmer, J., Pekkala, M., Catteau, J., Howard, N., Crock, P., Craig, M., Clarson, C. L., Bere, L., Thompson, D., Metzger, D., Kwan, J., Stephure, D. K., Pacaud, D., Ho, J., Schwarz, W., Girgis, R., Thompson, M., Catte, D., Daneman, D., Martin, M. -J., Morin, V., Frenette, L., Ferland, S., Sanderson, S., Heath, K., Huot, C., Gonthier, M., Thibeault, M., Legault, L., Laforte, D., Cummings, E. A., Scott, K., Bridger, T., Crummell, C., Newman, S., Houlden, R., Breen, A., Carson, G., Kelly, S., Sankaran, K., Penner, M., White, R. A., Hardy Brown, K., King, N., Popkin, J., Robson, L., Coles, K., Al Taji, E., Aldhoon, I., Mendlova, P., Vavrinec, J., Vosahlo, J., Brazdova, L., Venhacova, J., Venhacova, P., Cipra, A., Tomsikova, Z., Paterova, P., Gogelova, P., Einberg, U., Riikjarv, M. -A., Tillmann, V., Hirvasniemi, M., Kleemola, P., Parkkola, A., Suomalainen, H., Jarvenpaa, A. -L., Hamalainen, A. -M., Haavisto, H., Tenhola, S., Lautala, P., Salonen, P., Aspholm, S., Siljander, H., Holm, C., Ylitalo, S., Lounamaa, R., Nuuja, A., Talvitie, T., Lindstrom, K., Huopio, H., Pesola, J., Veijola, R., Tapanainen, P., Alar, A., Korpela, P., Kaar, M. -L., Mustila, T., Virransalo, R., Nykanen, P., Aschemeier, B., Danne, T., Kordonouri, O., Krikovszky, D., Madacsy, L., Khazrai, Y. M., Maddaloni, E., Pozzilli, P., Mannu, C., Songini, M., de Beaufort, C., Schierloh, U., Bruining, J., Basiak, A., Wasikowa, R., Ciechanowska, M., Deja, G., Jarosz-Chobot, P., Szadkowska, A., Cypryk, K., Zawodniak-Szalapska, M., Castano, L., Gonzalez Frutos, T., Oyarzabal, M., Serrano-Rios, M., Martinez-Larrad, M. T., Hawkins, F. G., Rodriguez Arnau, D., Ludvigsson, J., Smolinska Konefal, M., Hanas, R., Lindblad, B., Nilsson, N. -O., Fors, H., Nordwall, M., Lindh, A., Edenwall, H., Aman, J., Johansson, C., Gadient, M., Schoenle, E., Daftary, A., Klein, M. B., Gilmour, C., Malone, P., Tanner-Blasiar, M., White, N., Devaskar, U., Horowitz, H., Rogers, L., Colon, R., Frazer, T., Torres, J., Goland, R., Greenberg, E., Nelson, M., Schachner, H., Softness, B., Ilonen, J., Trucco, M., Nichol, L., Harkonen, T., Vaarala, O., and Luopajarvi, K.

Subjects
Canada, endocrine system diseases, infant feeding, breastfeeding, type 1 diabetes, breastfeeding duration, complementary feeding, infant formula, Infant, Article, United States, Diet, Nutrition Policy, Europe, Diabetes Mellitus, Type 1, Milk, Nutrition Assessment, Double-Blind Method, Surveys and Questionnaires, Animals, Humans, Infant Food, Prospective Studies, Infant Nutritional Physiological Phenomena
Abstract

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double-blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D-associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first-degree relative with T1D and increased human leukocyte antigen-conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.

Published
2017

81. Performance data of the new free-piston shock tunnel T5 at GALCIT

Author

Hornung, H, Sturtevant, B, Belanger, J, Sanderson, S, Brouillette, M, and Jenkins, M

Subjects
Research And Support Facilities (Air)
Abstract

A new free piston shock tunnel has been constructed at the Graduate Aeronautical Laboratories at Caltec. Compression tube length is 30 m and diameter 300 mm. Shock tube length is 12 m and diameter 90 mm. Piston mass is 150 kg and maximum diaphragm burst pressure is 130 MPa. Special features of this facility are that the pressure in the driver gas is monitored throughout the compression process until well after diaphragm rupture, and that the diaphragm burst pressure can be measured dynamically. An analysis of initial performance data including transient behavior of the flow over models is presented.

Published
1992

82. A drag measurement technique for free piston shock tunnels

Author

Sanderson, S. R, Simmons, J. M, and Tuttle, S. L

Subjects
Research And Support Facilities (Air)
Abstract

A new technique is described for measuring drag with 100-microsecond rise time on a nonlifting model in a free piston shock tunnel. The technique involves interpretation of the stress waves propagating within the model and its support. A finite element representation and spectral methods are used to obtain a mean square optimal estimate of the time history of the aerodynamic loading. Thus, drag is measured instantaneously and the previous restriction caused by the mechanical time constant of balances is overcome. The effectiveness of the balance is demonstrated by measuring the drag on cones with 5 and 15 deg semi-vertex angles in nominally Mach 5.6 flow with stagnation enthalpies from 2.6 to 33 MJ/kg.

Published
1991

84. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), Zimmermann, J. (Jakob), Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), and Zimmermann, J. (Jakob)

Published
2017
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88. A large-scale proteogenomics study of apicomplexan pathogens-Toxoplasma gondii and Neospora caninum

Author

Krishna, R, Xia, D, Sanderson, S, Shanmugasundram, A, Vermont, S, Bernal, A, Daniel-Naguib, G, Ghali, F, Brunk, B P, Roos, D S, Wastling, J M, and Jones, A R

Subjects
fungi, parasitic diseases, QR
Abstract

Proteomics data can supplement genome annotation efforts, for example being used to confirm gene models or correct gene annotation errors. Here, we present a large-scale proteogenomics study of two important apicomplexan pathogens: Toxoplasma gondii and Neospora caninum. We queried proteomics data against a panel of official and alternate gene models generated directly from RNASeq data, using several newly generated and some previously published MS datasets for this meta-analysis. We identified a total of 201 996 and 39 953 peptide-spectrum matches for T. gondii and N. caninum, respectively, at a 1% peptide FDR threshold. This equated to the identification of 30 494 distinct peptide sequences and 2921 proteins (matches to official gene models) for T. gondii, and 8911 peptides/1273 proteins for N. caninum following stringent protein-level thresholding. We have also identified 289 and 140 loci for T. gondii and N. caninum, respectively, which mapped to RNA-Seq-derived gene models used in our analysis and apparently absent from the official annotation (release 10 from EuPathDB) of these species. We present several examples in our study where the RNA-Seq evidence can help in correction of the current gene model and can help in discovery of potential new genes. The findings of this study have been integrated into the EuPathDB. The data have been deposited to the ProteomeXchange with identifiers PXD000297and PXD000298.

Published
2015

89. Quantification of CD4(+) T cell alloreactivity and its control by regulatory T cells using time lapse microscopy and immune synapse detection

Author

Juvet, S, Sanderson, S, Hester, J, Wood, K, and Bushell, A

Abstract

Assays designed to select transplant recipients for immunosuppression withdrawal have met with limited success, perhaps because they measure events downstream of T cell-alloantigen interactions. Using in vitro time lapse microscopy in a mouse transplant model we asked whether transplant outcome would result in changes in the proportion of CD4(+) T cells forming prolonged interactions with donor dendritic cells. By blocking CD4-MHC class II and CD28-B7 interactions, we defined immunologically relevant interactions as those ≥500s. Using this threshold, T cell-dendritic cell (T-DC) interactions were examined in rejection, tolerance and T cell control mediated by regulatory T cells. The frequency of T-DC contacts ≥500s increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. Regulatory T cells reduced prolonged T-DC contacts. Importantly, this effect was replicated with human polyclonally expanded naturally occurring regulatory T cells, which we have previously shown can control rejection of human tissues in humanized mouse models. Finally, in a proof-of-concept translational context, we have been able to visualize differential allogeneic immune synapse formation in polyclonal CD4(+) T cells using high-throughput imaging flow cytometry. This article is protected by copyright. All rights reserved.

Published
2015

94. Molecular adjuvant effects of a conformationally biased agonist of human C5a anaphylatoxin

Author

Tempero, R. M., Hollingsworth, M. A., Burdick, M. D., Angela Finch, Taylor, S. M., Vogen, S. M., Morgan, E. L., and Sanderson, S. D.

Subjects
Immunology, Immunology and Allergy
Abstract

A conformationally biased decapeptide agonist of human C5a anaphylatoxin (YSFKPMPLaR) was used as a molecular adjuvant in stimulating Ab responses against peptide epitopes derived from human MUC1 glycoprotein and the human mu and kappa opioid receptors. C57BL6 mice were immunized with the MUC1 epitope (YKQGGFLGL); the C5a agonist (YSFKPMPLaR); YSFKPMPLaR and YKQGGFLGL together, but unconjugated; a C5a-active, MUC1 epitope construct (YKQGGFLGLYSFKPMPLaR); and a C5a-inactive, reversed moiety construct (YSFKPMPLaRYKQGGFLGL). High Ab titers specific for the MUC1 epitope were observed only in mice immunized with the C5a-active epitope construct. Similar results were obtained in BALB/c mice immunized with the C5a-active, MUC1 epitope construct. Abs from the sera of the C57BL6 mice were predominately of the IgG2a, IgG2b, and IgM isotypes and were reactive against human recombinant MUC1 and MUC1 expressed by the Panc-1 M1F.15 pancreatic cell line. When compared with the corresponding KLH-epitope conjugates in C57BL6 mice, the epitope-C5a agonist constructs produced titers of specific IgG Abs of isotypes distinct from those generated by the keyhole limpet hemocyanin-epitope conjugates. Rabbits immunized with a mu opioid receptor epitope-C5a agonist construct (GDLSDPCGNRTNLGGRDSLYSFKPMPLaR) or a kappa opioid receptor epitope-C5a agonist construct (FPGWAEPDSNGSEDAQLYSFKPMPLaR) generated high titer, epitope-specific Ab responses. Ab titers generated in response to the opioid epitope-C5a agonist constructs were comparable to those generated by the opioid KLH-epitope conjugates. The results of this study are discussed in terms of possible mechanisms by which the conformationally biased C5a agonist serves as a molecular adjuvant.

Published
1997

96. Influence of heat input on friction stir welding for the ODS steel MA596

Author

Baker, B.W., Brewer, L.N., Menon, E.S.K., McNelley, T.R., El-Dasher, B., Torres, S., Farmer, J.C., Mahoney, M.W., Sanderson, S., Naval Postgraduate School (U.S.), and Mechanical and Aeronautical Engineering

Subjects
Friction stir welding, Oxide dispertion Strengthened Steel, MA596
Abstract

The oxide dispersion strengthened steel MA956 was friction stir welded using eight different rotational speed/translational speed combinations using a polycrystalline cubic boron nitride tool. Weld parameter conditions with high thermal input produced defect-free, full penetration welds. Electron backscatter diffraction showed a significant increase in grain size in the stir zone, a body centered cubic torsional texture in the stir zone, and a sharp transition in grain size across the thermo-mechanically affected zone. Micro-indentation results showed an asymmetric reduction in hardness across the transverse section of the weld that was sensitive to the heat input. This change in hardness is explained by the increase in grain size and may be described using a Hall-Petch type relationship. This work was sponsored by a collaborative research agreement between the Naval Postgraduate School and Lawrence Livermore National Laboratory.

Published
2013

97. Integration of swimming kinematics and ram suspension feeding in a model American paddlefish, Polyodon spathula.

Author

Haines, Grant E. and Sanderson, S. Laurie

Subjects
*FISH kinematics, *SWIMMING, *PADDLEFISH, *PREDATION, *FISH feeds, *ANIMAL behavior
Abstract

Ram suspension-feeding fishes swim with an open mouth to force water through the oral cavity and extract prey items that are too small to be pursued individually. Recent research has indicated that, rather than using a dead-end mechanical sieve, American paddlefish (Polyodon spathula) employ vortical cross-step filtration. In this filtration mechanism, vortical flow that is generated posterior to the branchial arches organizes crossflow filtration processes into a spatial structure across the gill rakers. Despite the known impact of locomotor kinematics on fluid flow around the bodies of swimming fish, the effects of locomotor kinematics on filtration mechanisms in ram suspension feeders are unknown. Potential temporal organization of filtration mechanisms in ram suspension-feeding fish has not been studied previously. We investigated the effects of locomotor kinematics associated with undulatory swimming on intraoral flow patterns and food particle transport. A mechanized model of the oral cavity was used to simulate the swimming kinematics of suspension-feeding paddlefish. We recorded fluctuations of flow speed and pressure within the model, which occurred at a frequency that corresponded with the frequency of the model's strides. Using the mechanized model in a flow tank seeded with Artemia cysts, we also showed that swimming kinematics aided the transport of this simulated food to the posterior margins of the gill slots, although the time scale of this transport is expected to vary with prey parameters such as size and concentration. Dye stream experiments revealed that, although stable vortical flow formed because of flow separation downstream of backward-facing steps in control trials, vortical flow structures in mechanized trials repeatedly formed and shed. These findings suggest strong integration between locomotor and feeding systems in ram suspension-feeding fishes. [ABSTRACT FROM AUTHOR]

Published
2017
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98. Taxonomic and nomenclatural rearrangements in Artemisia subgen. Tridentatae, including a redefinition of Sphaeromeria (Asteraceae, Anthemideae)

Author

Garcia, Sònia, Garnatje, Teresa, Durant McArthur, E., Pellicer, Jaume, Sanderson, S. C., and Vallès, Joan

Abstract

[EN]A recent molecular phylogenetic study of all members of Artemisia subgenus Tridentatae, as well as most of the other New World endemic Artemisia and the allied genera Sphaeromeria and Picrothamnus, raised the necessity of revising the taxonomic framework of the North American endemic Artemisia. Composition of the subgenus Tridentatae is enlarged to accommodate other North American endemics and is organized into 3 sections: Tridentatae, Nebulosae, and Filifoliae. This paper deals with the combination of one section, the amendment of 2 more sections, and the combination in or the reversion to Artemisia of some Sphaeromeria and Picrothamnus species. The new names given for previous Sphaeromeria species are Artemisia macarthurii (for S. argentea), A. albicans (for S. cana), A. constricta (for S. compacta), and A. inaequifolia (for S. diversifolia). The other Sphaeromeria we studied (S. capitata, S. potentilloides, S. ruthiae, and S. simplex) had been formerly considered Artemisia (respectively, A. capitata, A. potentilloides, A. ruthiae, and A. simplex), and their previous nomenclature is therefore recommended, [ES]Un estudio reciente sobre la filogenia molecular de todos los miembros del subgénero Tridentatae de Artemisia, así como de la mayoría de las otras especies de Artemisia endémicas del Nuevo Mundo y los géneros afines Sphaeromeria y Picrothamnus, hizo ver la necesidad de revisar el marco taxonómico de las especies de Artemisia endémicas a Norteamérica. La composición del subgénero Tridentatae se ha ampliado para dar cabida a las otras especies endémicas de Norteamérica, y está organizado en 3 secciones: Tridentatae, Nebulosae y Filifoliae. El presente artículo trata sobre la combinación de una sección y la enmienda de 2 más, y propone la incorporación o reversión a Artemisia de algunas especies de Sphaeromeria y Picrothamnus. Los nuevos nombres de las especies previamente asignadas a Sphaeromeria son Artemisia macarthurii (para S. argentea), A. albicans (para S. cana), A. constricta (para S. compacta) y A. inaequifolia (para S. diversifolia). Las otras especies de Sphaeromeria estudiadas (S. capitata, S. potentilloides, S.ruthiae y S. simplex) habían sido previamente consideradas como miembros de Artemisia (A. capitata, A. potentilloides, A. ruthiae y A. simplex, respectivamente), por lo quese recomienda utilizar su nomenclatura anterior, This work was subsidized by projects CGL2007-64839-C02-01/BOS and CGL2007-64839-C02-02/BOS of the Spanish government. SG was granted a JAE-DOC contract from the CSIC and a short stay in the Shrub Sciences Laboratory (USDA) in Utah, also from the CSIC.

Published
2011

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