15 results on '"Kananen, K."'
Search Results
2. Evidence for Multiple Teosinte Hybrid Zones in Central Mexico
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Sanchez-Gonzalez JdJ, Kananen K, John Doebley, David E. Hufnagel, Matthew B. Hufford, and Jeffrey C. Glaubitz
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education.field_of_study ,Taxon ,Hybrid zone ,Genus ,Range (biology) ,Evolutionary biology ,Population ,Biology ,education ,Isolation by distance ,Local adaptation ,Hybrid - Abstract
1SummaryHybrid zones provide an excellent opportunity for studying population dynamics and whether hybrid genetic architectures are locally adaptive. The genus Zea contains many diverse wild taxa collectively called teosinte.Zea maysssp.parviglumis, the lowland progenitor of maize (Zea maysssp.mays), and its highland relativeZea maysssp.mexicanalive parapatrically and, while putative hybrids have been identified in regions of range overlap, these have never been deeply explored.Here we use a broadly sampled SNP data set to identify and confirm 112 hybrids betweenZea maysssp.parviglumisandZea maysssp.mexicana, mostly clustered in three genetically and geographically distinct hybrid groups in Central Mexico.These hybrid groups inhabit intermediate environments relative to parental taxa. We demonstrate that these individuals are true hybrids and not products of isolation by distance or ancestral to parviglumis and mexicana. This work expands on previous studies, clearly identifying hybrid zones inZea, genetically characterizing hybrid groups, and showing what appear to be unique genetic architectures of hybridization in distinct hybrid groups.With the potential for local adaptation, variable hybrid zone dynamics, and differential architectures of hybridization, we present these teosinte hybrids and parental taxa as a promising model system for studying hybridization and hybrid zones.
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- 2021
3. Tuberoosiskleroosi - suomalainen diagnoosi- ja seurantasuositus
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Metsähonkala L, Alapulli H, Arvio M, Hiippala A, Hodgson U, Immonen A, Kananen K, Karvonen M, Kataja J, Kälviäinen R, Leppävirta J, Lähdesmäki T, Nisen H, Pöyhönen M, Vanninen R, Vasara K, Vieira P, and School of Medicine / Clinical Medicine
- Abstract
Tuberoosiskleroosia sairastavat potilaat tarvitsevat systemaattista, monen erikoisalan seurantaa läpi elämän. Tavoitteena on haitallisten tai jopa hengenvaarallisten elinmuutosten varhainen toteaminen ja hoito. Epilepsian tehokkaalla hoidolla ja kehityksen oikea-aikaisella tuella pyritään vaikuttamaan potilaiden kehitysennusteeseen ja neuropsykiatristen häiriöiden esiintymiseen. Tässä suosituksessa esitetään diagnosointi- ja seurantavaiheessa tarvittavat tutkimukset ja niiden toteutus, jossa hyödynnetään sekä erikoissairaanhoidon että perusterveydenhuollon palveluja., published version, peerReviewed
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- 2017
4. Koskikunnostusten vaikutukset ekosysteemipalveluihin kalastajien, melojien ja ranta-asukkaiden näkökulmasta Kiiminki-, Koston- ja Simojoella
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Kananen, K. (Kirsi)
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Geography - Abstract
Ihminen on vaikuttanut virtavesiin lähes koko historiansa ajan. Virtavesiä on muokattu mm. valjastamalla koskia sähköntuotantoon ja ruoppaamalla koskia taloudellisten tekijöiden vuoksi. Muokkaus on kaventanut virtavesien biodiversiteettiä. Tämä on johtanut tuottavuuden laskuun ja vaikuttanut kykyyn tuottaa ekosysteemipalveluita. Suomessa virtavesiä on muokattu lähinnä tukinuiton ja vesivoimatuotannon tarpeisiin. Virtavesikunnostukset ovat korjaavaa vesirakentamistoimintaa. Niiden avulla pyritään parantamaan joen nykyistä tilaa kohti luonnonmukaisempaa. Kunnostuksia on tehty pitkään lähinnä kalataloudellisista lähtökohdista. Joen muita käyttäjäryhmiä tai sosiaalisia seikkoja ei ole huomioitu samalla tavalla. Kunnostusvaikutusten arvioinnissa tarvitaan enemmän kokonaisvaltaista tutkimusta, jossa myös sosiaalinen näkökulma on aiempaa enemmän mukana. Tämän tutkielman tarkoituksena on tarkastella kysely- ja haastatteluaineiston kautta, kuinka virkistyskäyttäjät ja ranta-asukkaat kokevat ekosysteemipalveluiden muutoksen kolmella joella Pohjois-Suomessa. Lisäksi tarkastellaan, ovatko kunnostukset onnistuneet sekä mitä hyötyjä ja haittoja kunnostuksilla on eri käyttäjäryhmien näkökulmasta. Tutkielmassa käsitellään virtavesien ekosysteemipalveluita ja erityisesti kulttuuripalveluita, johon kuuluu merkittävänä osana virkistyspalvelut. Aineisto koostui melojien haastatteluista (n=10) sekä ranta-asukkaiden ja kalastajien kyselyistä (n= asukkaat 302 ja kalastajat 380). Vastauksia palautui yhteensä 682, jolloin vastausprosentti oli 31. Koskikunnostukset ovat edistäneet ranta-asukkaiden, kalastajien ja melojien kulttuuripalveluita, mutta tuotantopalveluihin kuuluvissa kalasaaliissa ei ole tapahtunut toivottua muutosta. Koskien kalastettavuus ja kalastuspaikat ovat käyttäjien mielestä parantuneet, mikä on vaikuttanut virkistyskäyttömahdollisuuksiin. Maisema koettiin muuttuneen kauniimmaksi ja luonnonmukaisemmaksi sekä äänimaisema miellyttävämmäksi. Tämä on todennäköisesti vaikuttanut myös asumisviihtyvyyteen, jonka koettiin parantuneen. Edellytykset virkistäytymiselle ovat yleisesti parantuneet ranta-asukkaiden ja kalastajien näkökulmasta, mutta jokien välillä oli eroavaisuuksia näiden kokemisessa. Toisaalta kulttuuripalveluiden hyödyntämismahdollisuudet ovat osittain vaikeutuneet. Uimisen harrastaminen on hieman hankaloitunut sekä koskissa kahlaaminen ja kalastaminen ovat joidenkin mielestä vaikeutuneet pyörivien kivien ja kuoppien takia. Kiveäminen ja uoman leventäminen ovat vaikeuttaneet melomista vähäisen veden aikaan. Melominen on voinut muuttua paikoin jopa mahdottomaksi. Osa melojista arvioi kuitenkin melomisen muuttuneen mielenkiintoisemmaksi. Kunnostukset eivät ole yleensä vaikuttaneet ranta-asukkaiden ja melojien vierailutottumuksiin, kun taas kalastajat ovat hieman lisänneet kalastusta kunnostusten jälkeen. Virkistyskäyttäjien ja ranta-asukkaiden mukaan jokiuoman kunnostukset eivät ole yksistään riittävä keino joen ekologisen tilan, virkistyskäytön ja asumisviihtyvyyden parantamiseksi. Heidän mielestään valuma-aluetasolla tarvitaan kokonaisvaltaisempaa ongelman hallintaa ja mm. turvetuotannon vaikutusten vähentämistä.
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- 2014
5. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes
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Parving, Hh, Brenner, Bm, Mcmurray, Jj, de Zeeuw, D, Haffner, Sm, Solomon, Sd, Chaturvedi, N, Persson, F, Desai, As, Nicolaides, M, Richard, A, Xiang, Z, Brunel, P, Pfeffer, Ma, Viberti, G, Lachin, Jm, Zinman, B, Pedersen, Tr, Villamil, As, Juncos, L, Prager, R, Verpooten, G, Zanella, Mt, Leiter, L, Pan, C, Wang, H, Botero, R, Cifkova, R, Christiansen, Js, Groop, Ph, Marre, M, Haller, H, Nickenig, G, Siamopoulos, K, Gero, L, Maggioni, A, Remuzzi, G, Katayama, Ss, Kim, Sg, Petrulioniene, Z, Lok, D, Kooy, A, Jorde, R, Medina, F, Polonia, J, Wong, Ks, Dukat, A, Rayner, Bl, Ruilope, L, Weiss, L, Wuethrich, R, Sheu, W, Sritara, P, Comlekci, A, Bilous, R, Toto, R, Jamerson, K, Carillo, E, Orias, M, Kuschnir, E, Rusculleda, M, Garcia, S, Farias, E, Lema, L, Hominal, M, Montaña, O, Sala, J, Diaz, M, Piskorz, D, Vita, N, Litwak, L, Sinay, I, Marin, M, Massari, P, Majul, C, Aizemberg, D, Azize, Gm, Bartolacci, I, Reboredo, A, Vico, M, Milesi, R, Sessa, H, Wassermann, A, Margulis, F, Zangroniz, P, Watschinger, B, Toplak, H, Paulweber, B, Drexel, H, Francesconi, C, Foeger, B, Mayer, G, Braun, Rk, Brath, H, Gaal, Lv, Niepen, Pv, Persu, A, Vercammen, C, Vriese, Ad, Coucke, F, Mathieu, C, Fery, F, Treille, S, Meeus, G, Acker, Kv, Scheen, A, Tits, J, Ruige, J, Krzesinski, Jm, Hollanders, G, Liénart, F, Dendale, P, Quinonez, M, Arnouts, P, Vanuytsel, J, Zanella, M, Mion D., Jr, Forti, A, Almeida, F, Cunha, R, de Paula RB, Brandao, A, Rocha, J, Krieger, E, Feitosa, G, Saraiva, J, Martin, J, Hissa, Mn, Schmid, H, Felicio, J, Sgarbi, J, Oigman, W, Bowering, K, Garceau, C, Berlingieri, Jc, Weisnagel, Sj, Hardin, P, Powell, C, Turcot, R, Muirhead, N, Aronson, R, Barima, Yt, Steele, Aw, Pandey, S, Woo, V, Cha, J, Dattani, D, Godin, C, Gupta, M, Saunders, K, Tellier, G, Ting, R, Tobe, S, Chouinard, G, Schlosser, R, Khandwala, H, Ekoe, Jm, Harris, Sb, Pichette, V, Lachance, P, Ooi, Tc, Tildesley, H, Barrett, B, Cournoyer, S, Lu, J, Zhang, H, Liu, X, Yan, S, Qi, X, Li, Q, Li, H, Lv, X, Yang, J, Sun, N, Xia, W, Wang, N, Tong, N, Mei, C, Gu, S, Zhang, J, Chen, X, Li, L, Su, B, Wang, L, Qiu, M, Wu, X, Liu, Z, Jia, W, Xu, G, Dong, J, Zhu, D, Zhang, M, Yan, J, Liu, B, Chen, J, Fu, J, Yan, L, Zhan, X, Zhong, L, Yang, T, Ma, J, Xu, M, Xu, X, Shi, B, Ji, Q, Zhong, H, He, R, Yuan, Z, Zhou, Z, Lin, H, Yang, W, Ke, Y, Hong, T, Franco, C, Casas, L, Triana, A, Jaramillo, C, Hernandez, E, Barrera, C, Blanco, D, Stipal, R, Widimsky, P, Dohnalova, L, Komroskova, M, Kvapil, M, Belobradkova, J, Tesar, V, Vodnansky, P, Kocourkova, B, Lervang, Hh, Perrild, H, Rossing, P, Oestergaard, O, Juhl, H, Thorsteinsson, B, Snorgaard, O, Urhammer, S, Egstrup, K, Tikkanen, T, Helin, K, Rinne, J, Lahtela, J, Strand, J, Valtonen, E, Saari, M, Kananen, K, Savela, K, Blacher, J, Aldigier, Jc, Zaoui, P, Fauvel, Jp, Gouet, D, Valensi, Pe, Charpentier, G, Marechaud, R, Penfornis, A, Ovize, M, Kovalchuck, Aa, Dellanna, F, Schoen, N, Groeschel, W, Eickhoff, F, Hanefeld, M, Merke, J, Rambausek, M, Zimmermann, U, Stuetz, W, Vosskuehler, A, Hevendehl, G, Schax, U, Lehmann, G, Haack, A, Hilgenberg, J, Klausmann, G, Adelberger, V, Gessner, S, Fiesselmann, A, Oerter, E, Hohenstatt, T, Groeschel, A, Behnke, T, Sisting, Rt, Schoch, D, Bieler, T, Schleyer, S, Altes, U, Klepzig, C, Rudofsky, G, Mueller, G, Burkhardt, F, Reschke, K, Senftleber, I, Wiesweg, Ck, Herrmann, Hj, Brandstetter, R, Segner, A, Schmitt, H, Rippert, R, Goebel, R, Schreibmueller, F, Pencz, I, Ott, P, Migdalis, I, Pappas, S, Pagkalos, E, Yalouris, A, Tsapas, A, Maltezos, E, Tentolouris, N, Papadakis, I, Ioannidis, G, Goumenos, D, Corona, V, Gonzalez, R, Haase, F, Monterroso, V, Sánchez, V, Turcios, E, Wyss, F, Arango, Jl, Bako, B, Deak, L, Dömötör, E, Dudas, M, Fulop, T, Kiss, I, Koranyi, L, Lengyel, Z, Nyirati, G, Oroszlan, T, Aniko, S, Vörös, P, Kapocsi, J, Wittmann, I, Paragh, G, Abraham, G, Tandon, N, Thomas, N, Mohan, V, Sahay, R, Sethi, B, Rao, V, Kumar, S, Chowdhury, S, Dharmalingam, M, Seshiah, V, Bantwal, G, Viswanathan, V, Yajnik, C, Adhikari, P, Krishnan, U, Varthakavi, P, Hiremath, J, Bhattacharyya, A, Dani, S, Modi, Kk, Glorioso, N, Morosetti, M, Veglio, Franco, Perticone, F, Dotta, F, Quarello, F, Sesti, G, Aiello, A, D'Ospina, A, Giordano, C, Novo, S, Santoro, A, Ferri, C, Capuano, V, Trimarco, B, Tonolo, G, Villa, G, De Pellegrin, A, Zanette, G, Federici, M, Aucello, G, Piatti, P, Vinciguerra, A, Mannarino, E, Taddei, S, Filetti, S, Grandaliano, G, Marchionni, N, Lambiase, C, Locatelli, F, Scanferla, F, Lembo, G, Leotta, S, Mos, L, Calatola, P, Fogari, R, David, S, Pedrinelli, R, Pignone, Am, Cozzolino, D, Bevilacqua, Mt, Catena, C, Del Prato, S, Cerasola, G, Frontoni, S, Falcone, C, Porta, A, Bonora, E, Cocchi, R, Fucili, A, Frisinghelli, A, Volpe, M, Carugo, S, Gambardella, S, Spagnuolo, V, Maglia, G, D'Angelo, Ar, Corsi, A, Limone, Pp, Guarnieri, A, Ghigo, Ezio, Ronchi, E, Ravera, M, Scioli, Ga, Sekiguchi, M, Aoki, S, Ogawa, Y, Seino, H, Onishi, Y, Tojo, A, Narimiya, M, Iwaita, Y, Takeda, H, Shimizu, H, Yamada, T, Kojima, S, Zushi, S, Kaneko, S, Matsumoto, A, Kajiyama, S, Fujita, H, Shikata, K, Tone, A, Matsubayashi, S, Tanaka, S, Sekigami, T, Tatsukawa, Y, Abe, N, Kawahara, K, Kasahara, H, Maeda, Y, Suzuki, Y, Okamoto, H, Tachi, K, Yamada, K, Uzu, T, Itou, T, Fukui, T, Kim, S, Kim, Y, Cho, W, Kwak, I, Chae, D, Oh, H, Ha, S, Shin, Y, Cha, D, Kang, S, Lim, C, Song, J, Kwon, Y, Badariene, J, Labutiniene, Ip, Zabuliene, L, Poteliuniene, V, Miglinas, M, van den Meiracker AH, Gregoor, Pj, Luik, Aj, van Loon BJ, Feenstra, Hj, Kaasjager, Ha, Viergever, Pp, Woittiez, Aj, van Bemmel, T, Lieverse, Ag, Simsek, S, Gaillard, Ca, van der Zwaan, C, Lok, Dj, Spiering, W, Nierop, Pr, Baggen, Mg, Leendert, Rj, de Jong, A, Leurs, Pb, Vincent, Hh, Wins, Eh, Voors, Aa, Ronner, E, Heeg, Je, van Hal JM, Boermans, T, Feis, Wl, Mostard, G, Bakker, Rc, Dunselman, Ph, Skeie, S, Istad, H, Skjelvan, G, Gronert, J, Tomala, T, Gudnason, S, Torvik, Dt, Risberg, K, Abedini, S, Cabrera, W, Medina, B, Herrada, B, Saavedra, A, Polonia, Dj, Providencia, Dl, Carvalho, D, Vasconcelos, Mp, da Silva GF, Branco, P, Gil, Dv, da Costa AG, da Silva PM, Arez, L, Martins, L, Birne, R, Dzuponova, J, Surovcikova, M, Culak, J, Filipova, S, Andre, I, Stevlik, J, Uhliar, R, Fabryova, L, Benacka, J, Koleny, D, Szentivanyi, M, Spisak, V, Pella, D, Pastrnakova, E, Martinka, E, Chua, T, Lau, T, Ng, Tg, Yeoh, Ly, Bhana, Sa, Rayner, B, Wellmann, H, Amod, A, Ranjith, N, Ahmed, F, Rheeder, P, Makan, H, Naicker, P, Podgorski, G, De Teresa, E, Olivan, J, Fernandez, Vl, Povedano, St, Terns, M, Ricart, W, Gonzalez, Jm, Fernandez, P, Parreño Lde, T, Redon, J, Parra, J, Calvo, C, Lopez, I, Puig, Jg, Calle, A, Garcia, Jc, Lopez, Jm, Jimenez, Ml, Fraile, B, Perez, Js, Nadal, Jj, Guija, E, Calviño, J, Barrios, V, Iglesias, Jn, Armario, P, Garcia, M, Aranda, P, Brotons, C, Gomez, P, Catelao, Am, Cusachs, Ar, Sarro, M, Martinez, V, dell Valle MH, Trias, F, Comas, A, Salvador, N, Martinez, F, Hernandez, F, Martinez, J, Mateos, C, Peral, Jl, Tolosana, J, Sobrino, J, Isart, J, Vizcaino, J, Vega, Ff, Zamorano, Jl, Bacariza, M, Soubriet, A, Fernández Cruz, A, Querejeta, R, Leira, Vm, Iglesias, Fe, Ibrik, O, Martin, D, Nanclares, Ms, Mediavilla, Jd, Galceran, Jm, Lopez, A, Muros, T, Pascual, J, Casalla, F, Tornero, F, Fernandez, G, Pettersson, P, Olsen, H, Franke, F, Stroembom, U, Furuland, H, Larnefelt, H, Allemann, Y, Krapf, R, Gerber, P, Munger, R, Hayoz, D, Graf, Hj, Burnier, M, Petrillo, A, Batt, R, Constam, En, Moccetti, T, Bianda, T, Rickli, H, Bulliard, C, Wu, Kd, Lin, Sh, Wu, Cj, Sheu, Wh, Su, Sl, Chen, Sc, Chou, Cw, Lee, Ct, Yang, Tc, Chen, Hc, Sukonthasarn, A, Sriratanasathavorn, C, Eiam Ong, S, Supasyndh, O, Chanchairujira, T, Kitiyakara, C, Arici, M, Usalan, C, Guneri, S, Koc, M, Kalender, B, Ates, K, Gurgun, C, Araz, M, Demirbas, B, Biernacki, W, Calvert, J, Eavis, P, Kerrane, J, Litchfield, J, Middleton, A, Roberts, J, Simpson, H, Charles, H, Jardine, A, Fisher, M, Banerjee, D, Gallen, I, Gnudi, L, Harvey, J, O'Hare, P, Vora, J, Winocour, P, Soran, H, Browne, D, Darko, D, Mancebo, Jg, de Roa ER, Antepara, N, Carrillo, E, Berrizbeitia, M, Guevara, L, Pernalete, N, Ontiveros, C, Zigrang, W, Blakney, E, Rosenblit, P, Weinstein, R, Klaff, L, Lipetz, R, Busick, E, Tung, P, Cooperman, M, Michael, S, Sun, Ch, Hart, T, Maddux, A, Bowden, R, East, C, Arakaki, R, Villafuerte, B, Mamish, Z, Mendez, R, Connery, L, Nour, K, Wynne, A, Busch, R, Zamora, B, Sachson, R, Prasad, J, Lasala, G, Smith, M, Fitz Patrick, D, Ruiz Rivera, L, Barranco, E, Solomon, R, Woolley, A, Brown, C, Freedman, Z, Schmidt, S, Pollock, J, Ruddy, M, Kopyt, Np, Bazzi, A, Horowitz, B, Feng, W, Wahl, T, Duprez, D, Gilbert, J, Steigerwalt, S, Jacqmein, J, Gorton, S, 3rd, Allison J., Pino, J, Lock, J, Leimbach, W, Anderson, J, Beacom, M, Craig, W, Gorson, D, Kerstein, H, Segal, S, Downey, H, Ledger, G, Mcgill, J, Gabriel, J, Nolen, T, Levinson, L, Williams, T, Levenson, D, Lerman, S, Minehart, C, Agarwal, N, Verma, S, Valitutto, M, Demetry, K, Mersey, J, Koeper, D, Fanti, P, Eng, G, Grimm, R, Fagan, T, Bajaj, M, Katz, L, Portnay, G, Altschuller, A, Desai, V, Bilazarian, S, Ipp, E, Rodelas, R, Burstein, D, Berg, J, Velez, J, Lund, R, Rekhi, A, Martin, E, Robertson, D, Singh, N, Narayan, P, Moustafa, M, Lanier, D, Seidner, M, Phillips, A, Vaughters, B, Sprague, A, Swartz, S, Lopez, R, Kumar, J, Bressler, P, Sadler, L, Wise, J, Kilbane, A., and Groningen Kidney Center (GKC)
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Male ,Hyperkalemia ,CARDIOVASCULAR MORTALITY ,BLOOD-PRESSURE ,Angiotensin-Converting Enzyme Inhibitors ,Type 2 diabetes ,GLOMERULAR-FILTRATION-RATE ,DOUBLE-BLIND ,chemistry.chemical_compound ,Fumarates ,cardiovascular disease ,Renin ,Treatment Failure ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,610 Medicine & health ,diabetes ,Medicine (all) ,Hazard ratio ,aliskiren ,diabete ,trial clinico ,Liter ,General Medicine ,Middle Aged ,hypertension ,Cardiovascular Diseases ,Combination ,HEART-FAILURE ,Drug Therapy, Combination ,Female ,Kidney Diseases ,type 2 diabetes ,medicine.symptom ,Type 2 ,medicine.medical_specialty ,Patient Dropouts ,Urology ,Hypokalemia ,Aliskiren ,chronic kidney disease ,Placebo ,Angiotensin Receptor Antagonists ,LEFT-VENTRICULAR DYSFUNCTION ,Drug Therapy ,Double-Blind Method ,Diabetes Mellitus ,medicine ,Humans ,CONVERTING-ENZYME INHIBITORS ,Antihypertensive Agents ,Aged ,Amides ,Diabetes Mellitus, Type 2 ,Follow-Up Studies ,business.industry ,medicine.disease ,Confidence interval ,Surgery ,Blood pressure ,MYOCARDIAL-INFARCTION ,chemistry ,SYSTOLIC DYSFUNCTION ,FOLLOW-UP ,business - Abstract
BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)
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- 2012
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6. Male gender explains increased birthweight in children born after transfer of blastocysts.
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Kaartinen, N. M., Kananen, K. M., Rodriguez-Wallberg, K. A., Tomás, C. M., Huhtala, H. S. A., Tinkanen, H. I., and Huhtala, H Sa
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BLASTOCYST , *EMBRYO transfer , *BIRTH weight , *HUMAN in vitro fertilization , *RETROSPECTIVE studies , *CASE-control method , *SELECTION bias (Statistics) , *COMPARATIVE studies , *CULTURE media (Biology) , *FERTILIZATION in vitro , *FREEZING , *RESEARCH methodology , *MEDICAL cooperation , *INDUCED ovulation , *RESEARCH , *SEX distribution , *EVALUATION research ,SEX differences (Biology) - Abstract
Study Question: Does extended embryo culture have a different effect on the birthweight of girls and boys?Summary Answer: The mean birthweight of boys born after fresh and frozen-thawed blastocyst transfer was increased compared with those born after cleavage stage embryo transfer. This effect was not detected among girls.What Is Known Already: Previous studies indicate that newborns from frozen-thawed cleavage stage embryos may present with a higher weight than newborns from fresh embryo transfers. With regard to fresh embryos, newborns after a blastocyst transfer have been reported as having higher birthweights than newborns from cleavage stage embryos.Study Design, Size, Duration: Retrospective multicentre case-control cohort study. All IVF/ICSI treatments were performed in the time-period from January 2008 to March 2014.Participants/materials, Setting, Methods: Birthweight of singletons born at full-term (≥37 weeks), after fresh or frozen blastocyst embryo transfers (n = 277), were compared with weights of children born after fresh or frozen cleavage stage embryo transfers (Day 2-3) (n = 277). The cases and controls were matched by delivery week, and by gender. Data of IVF/ICSI treatments, and the treatments' outcomes were collected and analysed.Main Results and the Role Of Chance: The birthweight after a fresh blastocyst transfer was significantly higher (mean 3530.6 g) than that after a transfer of cleavage stage embryos (mean 3418.8 g; weight difference 111.8 g, P = 0.047). The weights of newborns after frozen-thawed blastocyst transfers (mean 3647.5 g) and the frozen-thawed cleavage stage embryo transfers (mean 3650.9 g), were similar (weight difference 3.4 g, P = 0.95). The boys born after transfer of frozen-thawed blastocysts had a significantly higher birthweight (mean 3767.9 g) than girls (3525.2 g; weight difference 242.7 g, P = 0.002), whereas the difference of birthweights between genders was only 13.5 g in cleavage stage (P = 0.863). The same effect was seen after fresh blastocyst transfers (weight difference 211.5 g, P = 0.011), but not after fresh Day 2-3 embryo transfers (weight difference 53.6 g, P = 0.478).Limitations, Reasons For Caution: The study material was large enough to detect differences between birthweights as a whole, but a larger study group would confirm these new findings. To avoid selection bias, the next possible control candidate, fulfilling the selection criteria, was included for matching cases and controls. We have matched the cases and controls by gender and gestational week at birth, with an aim to reduce their impact as confounding factors.Wider Implications Of the Findings: Our findings of a similar weight at birth of newborns after frozen-thawed blastocysts and frozen-thawed cleavage stage embryos, when matching for age and duration of pregnancy, are novel. The gender of the newborn has an impact on the birthweight, and the extended embryo culture increases the weight difference between the genders, which is a new finding as well.Study Funding/competing Interests: The study was funded by the Fertility Society of Finland. [ABSTRACT FROM AUTHOR]- Published
- 2015
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7. A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes
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van Zuydam, Natalie R, Ahlqvist, Emma, Sandholm, Niina, Deshmukh, Harshal, Rayner, N William, Abdalla, Moustafa, Ladenvall, Claes, Ziemek, Daniel, Fauman, Eric, Robertson, Neil R, Mckeigue, Paul M, Valo, Erkka, Forsblom, Carol, Harjutsalo, Valma, Perna, Annalisa, Rurali, Erica, Marcovecchio, M Loredana, Igo, Robert P, Salem, Rany M, Perico, Norberto, Lajer, Maria, Käräjämäki, Annemari, Imamura, Minako, Kubo, Michiaki, Takahashi, Atsushi, Sim, Xueling, Liu, Jianjun, van Dam, Rob M, Jiang, Guozhi, Tam, Claudia H T, Luk, Andrea O Y, Lee, Heung Man, Lim, Cadmon K P, Szeto, Cheuk Chun, Wing Yee, So, Chan, Juliana C N, Ang, Su Fen, Dorajoo, Rajkumar, Wang, Ling, Clara, Tan Si Hua, Mcknight, Amy-Jayne, Duffy, Seamus, Pezzolesi, Marcus G, Marre, Michel, Gyorgy, Beata, Hadjadj, Samy, Hiraki, Koivula, S, Uggeldahl, T, Forslund, T, Halonen, A, Koistinen, A, Koskiaho, P, Laukkanen, M, Saltevo, J, Tiihonen, M, Forsen, M, Granlund, H, Jonsson, Ac, Nyroos, B, Kinnunen, P, Orvola, A, Salonen, T, Vähänen, A, Paldanius, Kr, Riihelä, M, Ryysy, L, Laukkanen, Kh, Nyländen, P, Sademies, A, Anderson, S, Asplund, B, Byskata, U, Liedes, P, Kuusela, M, Virkkala, T, Nikkola, A, Ritola, E, Niska, Tm, Saarinen, H, Oukko-Ruponen, Se, Virtanen, T, Lyytinen, Va, Kari, Ph, Simonen, T, Kaprio, Sa, Kärkkäinen, J, Rantaeskola, B, Kääriäinen, Tp, Haaga, J, Pietiläinen, Al, Klemetti, S, Nyandoto, T, Rontu, E, Satuli-Autere, S, Toivonen, Kr, Lansimaki, Hv, Ahonen, R, Ivaska-Suomela, M, Jauhiainen, A, Laine, Mm, Pellonpää, T, Puranen, R, Airas, Ma, Laakso, J, Rautavaara, K, Erola, Rm, Jatkola, E, Lönnblad, Tr, Malm, A, Mäkelä, J, Rautamo, E, Hentunen, P, Lagerstam, J, Feodoroff, M, Gordin, D, Heikkilä, O, Hietala, K, Fagerudd, J, Korolainen, M, Kyllönen, L, Kytö, J, Lindh, S, Pettersson-Fernholm, K, Rosengård-Bärlund, M, Sandelin, A, Thorn, L, Tuomikangas, J, Vesisenaho, T, Wadén, J, Sipilä, V, Kalliomäki, Ft, Koskelainen, J, Nikkanen, R, Savolainen, N, Sulonen, H, Valtonen, E, Norvio, L, Hämäläinen, A, Toivanen, E, Parta, Ja, Pirttiniemi, I, Aranko, S, Ervasti, S, Kauppinen-Mäkelin, R, Kuusisto, A, Leppälä, T, Nikkilä, K, Pekkonen, L, Jokelainen, Ks, Kananen, K, Karjalainen, M, Kemppainen, P, Mankinen, Am, Reponen, A, Sankari, M, Suominen, P, Lappalainen, A, Liimatainen, M, Santaholma, J, Aimolahti, A, Huovinen, E, Ilkka, V, Lehtimäki, M, Pälikkö-Kontinen, E, Vanhanen, A, Koskinen, E, Siitonen, T, Huttunen, E, Ikäheimo, R, Karhapää, P, Kekäläinen, P, Laakso, M, Lakka, T, Lampainen, E, Moilanen, L, Tanskanen, S, Niskanen, L, Tuovinen, U, Vauhkonen, I, Voutilainen, E, Rcw, Ma, Chan, Jcn, Huang, Y, Lan, Hy, Lok, S, Tomlinson, B, Tsui, Skw, Yu, W, Yip, Kyl, Chan, Tf, Fan, X, So, Wy, Szeto, Cc, Tang, N, Luk, Ao, Tian, X, Jiang, G, Tam, Cht, Lee, Hm, Lim, Ckp, Chan, Kkh, Xie, F, Acw, Ng, Cheung, Gpy, Yeung, Mw, Mai, S, Zhang, S, Yu, P, Weng, M, Maxwell, Ap, Mcknight, Aj, Savage, Da, Walker, J, Thomas, S, Viberti, Gc, Boulton, Ajm, Marshall, S, Demaine, Ag, Millward, Ba, Bain, Sc, Sandholm, N, Forsblom, C, Harjutsalo, V, Mäkinen, Vp, Ahola, Aj, Dahlström, E, Lehto, M, Lithovius, R, Panduru, Nm, Parkkonen, M, Saraheimo, M, Söderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, Lm, Tolonen, N, Groop, Ph, Mckay, Gj, Salem, Rm, Isakova, T, Palmer, C, Guiducci, C, Taylor, A, Mirel, Db, Williams, Ww, Hirschhorn, Jn, Florez, Jc, Brennan, Ep, Sadlier, Dm, Martin, F, Godson, C, Mayer, L, Gubitosi-Klug, R, Bourne, P, Schutta, M, Lackaye, Me, Gregory, Ns, Kruger, D, Jones, Jk, Bhan, A, Golden, E, Aiello, L, Larkin, M, Nathan, D, Ziegler, G, Caulder, S, Pittman, C, Luttrell, L, Lopes-Virella, M, Johnson, M, Gunyou, K, Bergenstal, R, Vittetoe, B, Sivitz, W, Flaherty, N, Bantle, J, Hitt, S, Goldstein, D, Hainsworth, D, Cimino, L, Orchard, T, Wigley, C, Dagogo-Jack, S, Strowig, S, Raskin, P, Barnie, A, Zinman, B, Fahlstrom, R, Palmer, J, Harth, J, Driscoll, M, Mcdonald, C, Lipps Hagan, J, May, M, Levandoski, L, White, N, Gatcomb, P, Tamborlane, W, Adelman, D, Colson, S, Molitch, M, Lorenzi, G, Mudaliar, S, Johnsonbaugh, S, Miller, R, Canady, J, Schade, D, Bernal, Ml, Malone, J, Morrison, A, Martin, C, Herman, W, Pop-Busui, R, Cowie, C, Leschek, E, Cleary, P, Lachin, J, Braffett, B, Steffes, M, Arends, V, Blodi, B, Danis, R, Lawrence, D, Wabers, H, Soliman, E, Zhang, Zm, Campbell, C, Hensley, S, Keasler, L, Mark, M, Albertini, M, Boustany, C, Ehlgen, A, Gerl, M, Huber, J, Schölch, C, Zimdahl-Gelling, H, Groop, L, Agardh, E, Ahlqvist, E, Ajanki, T, Al Maghrabi, N, Almgren, P, Apelqvist, J, Bengtsson, E, Berglund, L, Björckbacka, H, Blom-Nilsson, U, Borell, M, Burström, A, Cilio, C, Cinthio, M, Dreja, K, Dunér, P, Engelbertsen, D, Fadista, J, Gomez, M, Goncalves, I, Hedblad, B, Hultgårdh, A, Johansson, Me, Kennbäck, C, Kravic, J, Ladenvall, C, Lernmark, Å, Lindholm, E, Ling, C, Luthman, H, Melander, O, Neptin, M, Nilsson, J, Nilsson, P, Nilsson, T, Nordin, G, Orho-Melander, M, Ottoson-Laakso, E, Persson, A, Persson, M, Persson, Må, Postma, J, Pranter, E, Rattik, S, Sterner, G, Tindberg, L, Wigren, M, Zetterqvist, A, Åkerlund, M, Ostling, G, Kanninen, T, Ahonen-Bishopp, A, Eliasson, A, Herrala, T, Tikka-Kleemola, P, Hamsten, A, Betsholtz, C, Björkholm, A, Foroogh, F, Genové, G, Gertow, K, Gigante, B, He, B, Leander, K, Mcleod, O, Nastase-Mannila, M, Patrakka, J, Silveira, A, Strawbridge, R, Tryggvason, K, Vikström, M, Ohrvik, J, Österholm, Am, Thorand, B, Gieger, C, Grallert, H, Ludwig, T, Nitz, B, Schneider, A, Wang-Sattler, R, Zierer, A, Remuzzi, G, Benigni, A, Donadelli, R, Lesti, Md, Noris, M, Perico, N, Perna, A, Piras, R, Ruggenenti, P, Rurali, E, Dunger, D, Chassin, L, Dalton, N, Deanfield, J, Horsford, J, Rice, C, Rudd, J, Walker, N, Whitehead, K, Wong, M, Colhoun, H, Adams, F, Akbar, T, Belch, J, Deshmukh, H, Dove, F, Ellingford, A, Farran, B, Ferguson, M, Henderson, G, Houston, G, Khan, F, Leese, G, Liu, Y, Livingstone, S, Looker, H, Mccann, M, Mcgurnaghan, S, Morris, A, Newton, D, Pearson, E, Reekie, G, Smith, N, Shore, A, Aizawa, K, Ball, C, Bellenger, N, Casanova, F, Frayling, T, Gates, P, Gooding, K, Hattersley, A, Ling, R, Mawson, D, Shandas, R, Strain, D, Thorn, C, Smith, U, Hammarstedt, A, Häring, H, Pedersen, O, Sesti, G, Fagerholm, E, Toppila, I, Valo, E, Salomaa, V, Havulinna, A, Kristiansson, K, Okamo, P, Peltola, T, Perola, M, Pietilä, A, Ripatti, S, Taimi, M, Ylä-Herttuala, S, Babu, M, Dijkstra, M, Gurzeler, E, Huusko, J, Kholová, I, Merentie, M, Poikolainen, M, Mccarthy, M, Groves, C, Juliusdottir, T, Karpe, F, Lagou, V, Rayner, W, Robertson, N, van Zuydam, N, Cobelli, C, Di Camillo, B, Finotello, F, Sambo, F, Toffolo, G, Trifoglio, E, Bellazzi, R, Barbarini, N, Bucalo, M, Larizza, C, Magni, P, Malovini, A, Marini, S, Mulas, F, Quaglini, S, Sacchi, L, Vitali, F, Ferrannini, E, Boldrini, B, Kozakova, M, Mari, A, Morizzo, C, Mota, L, Natali, A, Palombo, C, Venturi, E, Walker, M, Patrono, C, Pagliaccia, F, Rocca, B, Nuutila, P, Haukkala, J, Knuuti, J, Roivainen, A, Saraste, A, Mckeague, P, Colombo, M, Steckel-Hamann, B, Bokvist, K, Shankar, S, Thomas, M, Gan, Lm, Heinonen, S, Jönsson-Rylander, Ac, Momo, R, Schnecke, V, Unwin, R, Walentinsson, A, Whatling, C, Nogoceke, E, Pacheco, Gd, Formentini, I, Schindler, T, Tortoli, P, Bassi, L, Boni, E, Dallai, A, Guidi, F, Lenge, M, Matera, R, Ramalli, A, Ricci, S, Viti, J, Jablonka, B, Crowther, D, Gassenhuber, J, Hess, S, Hubschle, T, Juretschke, Hp, Rutten, H, Sadowski, T, Wohlfart, P, Brosnan, J, Clerin, V, Fauman, E, Hyde, C, Malarstig, A, Pullen, N, Tilley, M, Tuthill, T, Vangjeli, C, Linda T, Ziemek D., Ahluwalia, Tarunveer S, Almgren, Peter, Schulz, Christina-Alexandra, Orho-Melander, Marju, Linneberg, Allan, Christensen, Cramer, Witte, Daniel R, Grarup, Niels, Brandslund, Ivan, Melander, Olle, Paterson, Andrew D, Tregouet, David, Maxwell, Alexander P, Lim, Su Chi, Ronald C W, Ma, Tai, E Shyong, Maeda, Shiro, Lyssenko, Valeriya, Tuomi, Tiinamaija, Krolewski, Andrzej S, Rich, Stephen S, Hirschhorn, Joel N, Florez, Jose C, Dunger, David, Pedersen, Oluf, Hansen, Torben, Rossing, Peter, Remuzzi, Giuseppe, Brosnan, Mary Julia, Palmer, Colin N A, Groop, Per-Henrik, Colhoun, Helen M, Groop, Leif C, Mccarthy, Mark, I, Palombo, Carlo, Clinicum, Diabetes and Obesity Research Program, Research Programs Unit, Nefrologian yksikkö, Department of Medicine, Institute for Molecular Medicine Finland, Tiinamaija Tuomi Research Group, Endokrinologian yksikkö, Per Henrik Groop / Principal Investigator, Leif Groop Research Group, HUS Abdominal Center, HUS Internal Medicine and Rehabilitation, and Lee Kong Chian School of Medicine (LKCMedicine)
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0301 basic medicine ,Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,LOCI ,Genome-wide association study ,Type 2 diabetes ,Bioinformatics ,Kidney Failure ,0302 clinical medicine ,Genome-wide analysis ,80 and over ,Diabetic Nephropathies ,Renal Insufficiency ,Chronic ,Genome-wide analysis, Type 2 Diabetes ,Aged, 80 and over ,RISK ,INSULIN-RESISTANCE ,diabetes ,Diabetes ,STAGE RENAL-DISEASE ,Single Nucleotide ,Middle Aged ,Type 2 Diabetes ,SUSCEPTIBILITY GENES ,Adult ,Aged ,Case-Control Studies ,Diabetes Mellitus, Type 2 ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Kidney Failure, Chronic ,Polymorphism, Single Nucleotide ,Renal Insufficiency, Chronic ,OBESITY ,BIOLOGICAL PATHWAYS ,nephropathy ,Medical genetics ,Type 2 ,kidney ,medicine.medical_specialty ,Diabetic Nephropathies/epidemiology ,Settore BIO/14 - FARMACOLOGIA ,Renal Insufficiency, Chronic/complications ,NEPHROPATHY ,SNP ,030209 endocrinology & metabolism ,Nephropathy ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Diabetes mellitus ,Journal Article ,Diabetes Mellitus ,Internal Medicine ,medicine ,Medicine [Science] ,Polymorphism ,Diabetic Kidney Disease ,METAANALYSIS ,Genetic heterogeneity ,business.industry ,Diabetes Mellitus, Type 2/complications ,association ,Case-control study ,nutritional and metabolic diseases ,Kidney Failure, Chronic/complications ,FAT DISTRIBUTION ,medicine.disease ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Microalbuminuria ,genetic ,business - Abstract
Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore)
8. Adaptive adjustment of significance thresholds produces large gains in microbial gene annotations and metabolic insights.
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Kananen K, Veseli I, Quiles Pérez CJ, Miller S, Eren AM, and Bradley PH
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Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes. Our results show that by adaptively tuning sequence similarity thresholds, sensitivity can be substantially improved while maintaining accuracy. We observe the largest improvements when few reference sequences exist for a given protein family, and when annotating genomes from non-model organisms (such as gut-dwelling Lachnospiraceae). Our results suggest that straightforward heuristic adjustments can broadly improve microbial metabolic predictions.
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- 2024
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9. Healthy live birth following embryo transfer of a blastocyst of tetrapronuclear (4PN) origin: a case report.
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Bredbacka P, Capalbo A, Kananen K, Picchetta L, and Tomás C
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- Pregnancy, Humans, Female, Male, Fertilization in Vitro methods, Embryo Transfer, Genetic Testing methods, Aneuploidy, Blastocyst, Live Birth, Preimplantation Diagnosis methods
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During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies. Nonetheless, the inclusion of genotyping data in preimplantation genetic testing has revealed that a normal diploid configuration is possible in embryos deriving from zygotes with an abnormal pronuclei number such as tripronuclear and one pronucleus. Here, we present a one-of-a-kind transfer of a tetrapronuclear-derived embryo that was discovered to be diploid and negative for other whole chromosome or segmental aneuploidies during preimplantation genetic testing using a targeted next-generation sequencing approach. The transfer resulted in the live birth of a healthy infant who is now 4 years old and has no apparent health or developmental impairments., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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10. Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses' health study.
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Asad S, Damicis A, Heng YJ, Kananen K, Collier KA, Adams EJ, Kensler KH, Baker GM, Wesolowski R, Sardesai S, Gatti-Mays M, Ramaswamy B, Eliassen AH, Hankinson SE, Tabung FK, Tamimi RM, and Stover DG
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- Humans, Female, Adolescent, Body Mass Index, Diet, Biomarkers, Genomics, Tumor Microenvironment, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Nurses
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Background: Breast tumor immune infiltration is clearly associated with improved treatment response and outcomes in breast cancer. However, modifiable patient factors associated with breast cancer immune infiltrates are poorly understood. The Nurses' Health Study (NHS) offers a unique cohort to study immune gene expression in tumor and adjacent normal breast tissue, immune cell-specific immunohistochemistry (IHC), and patient exposures. We evaluated the association of body mass index (BMI) change since age 18, physical activity, and the empirical dietary inflammatory pattern (EDIP) score, all implicated in systemic inflammation, with immune cell-specific expression scores., Methods: This population-based, prospective observational study evaluated 882 NHS and NHSII participants diagnosed with invasive breast cancer with detailed exposure and gene expression data. Of these, 262 women (training cohort) had breast tumor IHC for four classic immune cell markers (CD8, CD4, CD20, and CD163). Four immune cell-specific scores were derived via lasso regression using 105 published immune expression signatures' association with IHC. In the remaining 620 patient evaluation cohort, we evaluated association of each immune cell-specific score as outcomes, with BMI change since age 18, physical activity, and EDIP score as predictors, using multivariable-adjusted linear regression., Results: Among women with paired expression/IHC data from breast tumor tissue, we identified robust correlation between novel immune cell-specific expression scores and IHC. BMI change since age 18 was positively associated with CD4+ (β = 0.16; p = 0.009), and CD163 novel immune scores (β = 0.14; p = 0.04) in multivariable analyses. In other words, for each 10 unit (kg/m
2 ) increase in BMI, the percentage of cells positive for CD4 and CD163 increased 1.6% and 1.4%, respectively. Neither physical activity nor EDIP was significantly associated with any immune cell-specific expression score in multivariable analyses., Conclusions: BMI change since age 18 was positively associated with novel CD4+ and CD163+ cell scores in breast cancer, supporting further study of the effect of modifiable factors like weight gain on the immune microenvironment., (© 2022. The Author(s).)- Published
- 2022
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11. Real-world treatment outcomes in multiple myeloma: Multicenter registry results from Finland 2009-2013.
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Remes K, Anttila P, Silvennoinen R, Putkonen M, Ollikainen H, Terävä V, Sinisalo M, Kananen K, Schain F, Castren-Kortegangas P, Järvinen TM, Pisini M, Wahl F, Dixon T, and Leval A
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- Aged, Aged, 80 and over, Female, Finland, Humans, Kaplan-Meier Estimate, Middle Aged, Multiple Myeloma mortality, Registries, Retrospective Studies, Transplantation, Autologous, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
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Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data., Methods: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009-2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status., Results: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively., Conclusions: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale., Competing Interests: KR has been a member of Advisory Boards for Abbvie, Celgene, Janssen-Cilag and Takeda and has received fees to attend Congresses from Abbvie, Amgen, Celgene, Janssen-Cilag, Sanofi, Takeda. PA has been a member of Advisory Boards for Amgen, Celgene, Janssen and Takeda and has received fees to attend Congresses from Amgen, Bristol-Meyers-Squibb, Celgene, Janssen, Roche, Sanofi, Takeda and Teva. RS has received research funding from Amgen, BMS, Celgene, Janssen-Cilag and Takeda and honoraria from the same companies (Advisory Board and presentations). MP has received honoraria from Amgen, Celgene, Janssen-Cilag and Takeda (Advisory Board and presentations). HO does not have any competing interests. VT does not have any competing interests. MS does not have any competing interests. KK has received financial support from Jansen to collect data for this study and travel grants from Amgen, Shire and Sanofi Genzyme. TJ, MaP, FS, PCK and AL are employees of Janssen, the funder of this research. FW does not have any competing interests. TD is a Director of JB Medical and has worked with, and been funded by, other pharmaceutical companies in the field of hematological cancer. The funder Janssen provided support in the form of salaries for authors AL, PCK, TMJ, FS, MaP. This was a company sponsored study conducted in collaboration with the Finnish researchers, where both parties were involved in the study design, analysis and publication as per ICMJE standards. Data collection was carried out at the Finnish hospitals, with financial support from the funder. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Janssen funded JB Medical Ltd to provide medical writing support, TD is a paid employee of JB Medical and carried out the work. JB Medical did not have any additional role in the study design, data collection and analysis or decision to publish. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2018
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12. Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate.
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Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, and Välimäki MJ
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- Adult, Aged, Bone Density, Bone Remodeling, Female, Humans, Male, Middle Aged, Pamidronate, Transplantation, Homologous, Calcium Carbonate administration & dosage, Diphosphonates therapeutic use, Gonadal Steroid Hormones therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hormone Replacement Therapy, Osteoporosis prevention & control, Vitamin D administration & dosage
- Abstract
Context: In controlled studies, bisphosphonates have been used to prevent bone loss after solid organ transplantations but not in conjunction with stem cell transplantation (SCT)., Objective: The objective of the study was to test whether additional iv pamidronate would prevent bone loss associated with SCT more effectively than the combination of calcium, vitamin D, and sex steroid replacement therapy alone., Setting: The study was carried out at the Helsinki University Central Hospital. PATIENTS, DESIGN, INTERVENTION: Ninety-nine adult recipients of allogeneic SCT were randomized by age and gender into two groups. In one group, the patients received 1000 mg calcium carbonate and 800 IU vitamin D daily, and females received estrogen and males received testosterone replacement therapy. In another group, the patients received the same treatments plus six iv infusions of 60 mg pamidronate before and 1, 2, 3, 6, and 9 months after SCT., Main Outcome Measures: Bone mineral density (BMD) of the lumbar spine and the upper femur, measured by dual-energy x-ray absorptiometry, and bone turnover markers were followed for 12 months., Results: In the pamidronate group, lumbar spine BMD remained stable but decreased in the other group by 2.9% at 12 months (P = 0.0084 between the groups over time). Total hip BMD reduced 5.1% in the pamidronate group and 7.8% in the other group by 12 months (P = 0.0015), and femoral neck BMD reduced 4.2 and 6.2%, respectively (P = 0.074). In the pamidronate group, serum type I procollagen amino-terminal propeptide (P = 0.032 between the groups over time) and urinary type I collagen amino-terminal telopeptide (P = 0.035) decreased 79 and 68% during the first 3 months, and remained lowered thereafter, but did not change in the other group., Conclusions: The recipients of allogeneic SCT receiving additional pamidronate sustain less bone loss than those treated with calcium, vitamin D, and sex steroid replacement alone. Despite all the efforts, however, bone loss is not totally abolished at the hip.
- Published
- 2005
- Full Text
- View/download PDF
13. Direct luteinizing hormone action triggers adrenocortical tumorigenesis in castrated mice transgenic for the murine inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene.
- Author
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Rilianawati, Paukku T, Kero J, Zhang FP, Rahman N, Kananen K, and Huhtaniemi I
- Subjects
- Adrenal Cortex Neoplasms physiopathology, Animals, Antigens, Polyomavirus Transforming genetics, Castration, Cell Transformation, Neoplastic genetics, Chorionic Gonadotropin pharmacology, Crosses, Genetic, DNA Replication drug effects, Female, Gonadal Steroid Hormones pharmacology, Gonadotropin-Releasing Hormone analogs & derivatives, Gonadotropin-Releasing Hormone toxicity, Gonadotropins, Pituitary deficiency, Granulosa Cell Tumor physiopathology, Humans, Leydig Cell Tumor physiopathology, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Mutant Strains, Mice, Transgenic, Neoplasms, Hormone-Dependent physiopathology, Organ Specificity, Ovarian Neoplasms physiopathology, Peptides genetics, Receptors, FSH analysis, Receptors, LH biosynthesis, Receptors, LH physiology, Recombinant Fusion Proteins physiology, Simian virus 40 physiology, Testicular Neoplasms physiopathology, Thecoma physiopathology, Tumor Cells, Cultured, Adrenal Cortex Neoplasms genetics, Antigens, Polyomavirus Transforming physiology, Granulosa Cell Tumor genetics, Inhibins, Leydig Cell Tumor genetics, Luteinizing Hormone pharmacology, Luteinizing Hormone physiology, Neoplasms, Hormone-Dependent genetics, Ovarian Neoplasms genetics, Peptides physiology, Promoter Regions, Genetic, Testicular Neoplasms genetics, Thecoma genetics
- Abstract
Transgenic (TG) mice, expressing the Simian Virus 40 T-antigen (Tag) under a 6-kb fragment of the murine inhibin alpha-subunit promoter (inh alpha p), develop gonadal tumors of granulosa/theca or Leydig cell origin. We showed previously that adrenocortical tumors develop if the TG mice are gonadectomized but never develop in intact animals. However, if functional gonadectomy was induced by GnRH antagonist treatment or by cross-breeding the TG mice into the hypogonadotropic hpg genetic background, neither gonadal nor adrenal tumors appeared. Since the most obvious difference between the gonadectomized and GnRH-antagonist-treated or Tag/hpg double mutant mice is the elevated gonadotropin secretion in the first group, we examined whether the adrenal tumorigenesis would be gonadotropin-dependent. Surprisingly, both the adrenal tumors and a cell line (C alpha 1) derived from one of them expressed highly functional LH receptors (LHR), as assessed by Northern hybridization, immunocytochemistry, ligand binding, and human CG (hCG)-stimulated cAMP and steroid production. No FSH receptor expression was found in the adrenal tumors by RT-PCR. hCG treatment of the C alpha 1 cells stimulated their proliferation, as measured by [3H]thymidine incorporation. This effect was related to hCG-stimulated steroidogenesis since progesterone, testosterone, and estradiol, at physiological concentrations, also stimulated the C alpha 1 cell proliferation. Different adrenocortical cells expressed initially LHR and Tag, whereas both were highly expressed in the tumor cells. In conclusion, the high level of functional LHR in the adrenal tumors indicates that this receptor can function as tumor promoter when ectopically expressed and stimulated by the ligand hormone.
- Published
- 1998
- Full Text
- View/download PDF
14. Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene.
- Author
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Kananen K, Rilianawati, Paukku T, Markkula M, Rainio EM, and Huhtaniemi I
- Subjects
- Animals, Antigens, Polyomavirus Transforming analysis, Disease Models, Animal, Female, Gonadotropin-Releasing Hormone analogs & derivatives, Gonadotropin-Releasing Hormone pharmacology, Gonadotropins metabolism, Hormone Antagonists pharmacology, Hyperplasia, Leydig Cells chemistry, Leydig Cells pathology, Male, Mice, Mice, Transgenic, Ovarian Neoplasms blood, Ovarian Neoplasms genetics, Ovary pathology, Peptides analysis, Peptides blood, Pituitary Gland chemistry, Progesterone analysis, Progesterone blood, Promoter Regions, Genetic genetics, RNA, Messenger analysis, RNA, Messenger genetics, Testicular Neoplasms blood, Testicular Neoplasms genetics, Testis pathology, Testosterone analysis, Testosterone blood, Time Factors, Antigens, Polyomavirus Transforming genetics, Cell Transformation, Neoplastic drug effects, Cloning, Molecular, Gonadotropins antagonists & inhibitors, Inhibins, Ovarian Neoplasms pathology, Peptides genetics, Testicular Neoplasms pathology
- Abstract
We have previously developed a transgenic (TG) mouse model expressing the Simian virus 40 T-antigen (Tag), driven by a 6-kb fragment of the mouse inhibin alpha-subunit promoter (inh-alpha). The mice develop metastasizing gonadal tumors, of granulosa/theca or Leydig cell origin, with 100% penetrance by the age of 5-8 months. In the present study, we examined whether the appearance and growth of the gonadal tumors are dependent on gonadotropins. Gonadotropin suppression was achieved either by treatment of 3-month-old mice for 2-3 months with a GnRH antagonist (Cetrorelix, SB-75), or by cross-breeding the TG mice to the genetic background of the gonadotropin-deficient hypogonadal mutant mouse (hpg). Gonadal tumor growth was clearly inhibited by SB-75 treatment in one of the TG mouse lines (IT6-M), as indicated by the absence of macroscopically visible tumors and by reduced gonadal weights. Despite the suppressed gonadotropin secretion and Tag expression, hyperplasia of testicular Leydig, and ovarian stromal cells persisted in some of the treated mice. In another TG mouse line (IT6-F), with more aggressive tumorigenesis, the SB-75 treatment only partially inhibited gonadal tumor growth. None of the hypogonadotropic TG mice, homozygous for the hpg mutation, developed gonadal tumors. Their gonadal histology was indistinguishable from that of the non-TG hpg mice, suggesting total inhibition of gonadal tumorigenesis in the absence of gonadotropin stimulation. Tag expression and Leydig cell hyperplasia were apparent already in the postnatal TG mice but absent in those TG mice homozygous for the hpg mutation. In conclusion, the present results indicate that the gonadal tumorigenesis in our TG mouse model starts in early age as hyperplasia in specific somatic cells. Both this, and the subsequent malignant tumor growth, are gonadotropin dependent. A sufficient level of Tag expression, a prerequisite for gonadal tumorigenesis, only occurs upon gonadotropin stimulation.
- Published
- 1997
- Full Text
- View/download PDF
15. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera.
- Author
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Hämäläinen KM, Kananen K, Auriola S, Kontturi K, and Urtti A
- Subjects
- Absorption, Animals, Aqueous Humor metabolism, Chromatography, High Pressure Liquid, Diffusion Chambers, Culture, Epithelium metabolism, Female, Male, Mass Spectrometry, Molecular Weight, Porosity, Rabbits, Cell Membrane Permeability physiology, Conjunctiva metabolism, Cornea metabolism, Pharmaceutic Aids pharmacokinetics, Polyethylene Glycols pharmacokinetics, Sclera metabolism
- Abstract
Purpose: To characterize quantitatively the paracellular permeation routes in rabbit cornea, conjunctiva, and sclera using polyethylene glycol (PEG) oligomers., Methods: Corneal, conjunctival, and scleral tissues from New Zealand white rabbits were tested individually in a modified two-chamber Ussing apparatus with the mixture of PEGs with mean molecular weights 200, 400, 600, and 1000 in glutathione bicarbonated Ringer's solution buffer on the donor side of the chamber. The samples and standards were analyzed with high-performance liquid chromatography-thermospray mass spectrometry method. The pore sizes and the pore densities of the corneal and conjunctival epithelia were calculated using an effusion-like approach., Results: The conjunctival and scleral tissues were 15 to 25 times more permeable than the cornea and the molecular size affected the conjunctival permeability less than that of the cornea. The palpebral and bulbar conjunctivas had equal permeabilities. The scleral permeability was approximately half of that in the conjunctiva and approximately 10 times more than in the cornea. The conjunctival epithelia had 2 times larger pores and 16 times higher pore density than the cornea. The total paracellular space in the conjunctiva was estimated to be 230 times greater than that in the cornea., Conclusions: The conjunctival epithelium, due to its higher membrane permeability and larger absorptive and intercellular space surface areas, is the most viable route for ocular delivery of peptides and oligonucleotides.
- Published
- 1997
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