32 results on '"Hulme L."'
Search Results
2. Hormonal Contraceptive Use and Cycle Phase Effects on Competitive Persistence: Progesterone as a Mediating Mechanism (Stage 1 Registered Report)
- Author
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Kathleen V. Casto, Arthur-Hulme L, and Khandis R. Blake
- Subjects
Contraceptive use ,business.industry ,Mechanism (biology) ,Medicine ,Physiology ,business ,Persistence (computer science) ,Hormone - Abstract
Objectives: Increasing evidence suggests that hormonal contraceptive (HC) use adversely effects psychological functioning and competitiveness. HCs expose women to consistently high doses of synthetic progesterone, a hormone that fluctuates across the natural menstrual cycle. We propose to test group differences in competitive persistence between HC users, naturally cycling (NC) women in their low progesterone phase, and NC women in their high progesterone phase. Additionally, we will test salivary progesterone among NC women as a mediator of phase effects on competitiveness.Method: Pre-screening will identify HC users, and naturally cycling women at the two cycle phases. Participants will provide a sample of saliva and complete two behavioral competitiveness tasks. Covariates will also be collected.Predicted Results: We predict that follicular phase NC women will demonstrate longer competitive persistence compared to luteal phase NC women and HC users. Progesterone will positively mediate the effect of cycle phase on competitive persistence among NC women. Conclusions: This research will address the effects of HC use, cycle phase, and progesterone levels on competitive behavior in women. The outcome may be an artifact of female reproductive physiology that is likely adaptive, but potentially detrimental to women’s social and occupational advancement, raising concerns about the social-psychological risks of HC use.
- Published
- 2021
- Full Text
- View/download PDF
3. PMS4 Comparative Efficacy of Filgotinib Versus Alternative Treatments for Rheumatoid Arthritis in Patients with an Inadequate Response to Methotrexate: A Systematic Review and Network Meta-Analysis
- Author
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Jacob, I., primary, Beresford-Hulme, L., additional, Butler, K., additional, McNamara, B., additional, Dennis, J., additional, Baker, J., additional, Hayward, O., additional, Sadler, S., additional, Sugrue, D., additional, Gordon, J., additional, Radford, M., additional, Gharaibeh, M., additional, and L.U., X., additional
- Published
- 2020
- Full Text
- View/download PDF
4. An evaluation of the practicability and potential cost-effectiveness of providing a Relenza influenza treatment programme for employees through Occupational Health at UK Glaxo Wellcome sites
- Author
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Scott, A. J., Cunningham-Hill, M., Elliot, P., and Hulme, L. R.
- Published
- 2002
5. PDB96 THE IMPACT OF ADJUNCT DAPAGLIFLOZIN ON TREATMENT SATISFACTION IN TYPE 1 DIABETES MELLITUS
- Author
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Gordon, J., primary, Beresford-Hulme, L., additional, Bennett, H., additional, Tank, A., additional, Edmonds, C., additional, and McEwan, P., additional
- Published
- 2019
- Full Text
- View/download PDF
6. G384(P) A quality improvement (qi) project to increase the number of ventilated days between unplanned extubations within paediatric intensive care – using real time statistical monitoring
- Author
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Russell, M, primary, Alexander, J, additional, and Hulme, L, additional
- Published
- 2015
- Full Text
- View/download PDF
7. Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease.
- Author
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Reaich R., Schouten D., Rashid H., Birtcher K., Cantu J., Tait C., Taun W., Fadem S., Das D., Khosla U., Brown C., Brown T., Buquing J., Cromwell H., Dickson N., Najimipour B., Robeson J., Tabibi W., Mulloy L., Bailey K., Burton B., Fall P., Jagadeesan M., Paulson W., Szerlip H., White J., Faulkner M., Adeleye O., Boatright D., Mensah D., Nwankwo U., Crutcher L., Cummings C., Floyd M., Putatunda B., Ross J., Sanford V., Thadani U., Haragsim L., Parker B., Rogan L., Thresher M., Turner J., Dworkin L., Mignano D., O'Mara A., Shemin D., Bakris G., Basta E., Chua D., Neri G., Ahmed I., Elliott W., Fondren L., Hasabou N., Khosla N., Mazin A., Riehle J., Kovesdy C., Mendoza J., Ahmadzadeh S., Iranmanesh A., Lewis M., Lu J., Benabe J., Gonzalez-Melendez E., Padilla B., Serrano J., Russ T., Athmann L., Funke L., Larson P., Roach D., Salveson B., Nogueira J., Hanes D., Hise M., Light P., Copland E., Fink J., Hakim M., Hough K., McMinn S., Weir M., Young C., Kershaw G., Hill I., White B., Plumb T., Florescu M., Groggel G., Martin M., Rao V., Denu-Ciocca C., Candiani C., Cooper J., Gordon B., Joy M., Kiser M., Lambeth C., Rosas S., Cochetti P., Robinson J., Schankel K., Teng H., Weise W., Geneidy A., Murray P., Solomon R., De Waal D., LaPointe S., Schoenknecht A., Campese V., Habashy M., Ananthakrisna R., Bedwani D., Fazli U., Fetrat M., Frampton Q., Kaldas B., Kazarian V., Pitts L., Sadeghi A., Yeasmin N., Young E., Fissell R., Belanger K., Ricci N., Farwell W., Bowman T., Dhingra R., Pesenson A., Ambrosino J., Chittamooru S., Kaufman J., Ramos M., Yap C., Nakhle S., Aligaen L., Duren D., Laine B., Moore S., Tuazon H., Coyne D., Audrain J., Bryant B., Dombek S., Freeman S., Klein P., Germain M., Berkowitz A., Bokhari A., Braden G., Diaz A., Greco B., Mulhern J., O'Shea M., Poindexter A., Poppel D., Ryan M., Sweet S., Ye J., Osterman J., Lin T., Mays B., Rizvi A., Sonnier C., Twining C., Wang S., Hix M., Schenck J., Baigent C., Landray M., Reith C., Dasgupta T., Emberson J., Herrington W., Lewis D., Mafham M., Collins R., Bray C., Chen Y., Baxter A., Young A., Hill M., Knott C., Cass A., Feldt-Rasmussen B., Fellstrom B., Grobbee R., Gronhagen-Riska C., Haas M., Holdaas H., Hooi L.S., Jiang L., Kasiske B., Krairittichai U., Levin A., Massy Z., Tesar V., Walker R., Wanner C., Wheeler D., Wiecek A., Majoni W., Simpson D., Strony J., Musliner T., Agodoa L., Armitage J., Chen Z., Craig J., De Zeeuw D., Gaziano M., Grimm R., Krane V., Neal B., Ophascharoensuk V., Pedersen T., Sleight P., Tobert J., Tomson C., Sandercock P., Keech A., Whelton P., Yusuf S., Peto R., Parish S., Dolph L., Bahu T., Booth-Davey E., Brewster A., Yau F., Denis E., Frederick K., Haywood D., Heineman J., Howard S., Jayne K., Madgwick Z., Michell S., Murphy K., Ning L., Nolan J., Nunn M., Roberts J., Wickman M., Bowman L., Bulbulia R., Haynes R., Rahimi K., Rahman N., Ait-Sadi R., Barton I., Zhu W., Clark S., Kourellias K., Radley M., Brown K., Worthing D., Coates G., Goodenough B., Lucas N., Carreras A., Currie R., Donaldson O., Fjalling E., Gallagher M., Gibson K., Goddard J., Healy J., Hones L., Jardine M., Kwong I., Merai M., Murray S., Perkovic V., Rendina A., Gallo K., Caron S., Carlson K., Foley K., Matzek S., Mewhort L., O'Donoghue S., Perel-Winkler A., Terins T., Nie Q., Yu H., Ge L., Hao D., Li L., Pang X., Wei X., Yan G., Certikova Chabova V., Holst H., Molvadgaard T., Munksgaard D., Peltonen Y., Liabeuf S., Lebel C., Ouabou L., Bauer B., Bergmann K., Beusch M., Cavitt D., Drechsler C., Dulau I., Hugen K., Kempf S., Kuchenmeister B., Pscheidl V., Schmiedeke D., Schwarz M., Speerschneider K., Stahl B., Lim B.C., Nadia H., Zishareena M.F., Vasuthavan S., Ganesapillai A.T., Yuen S., Grobbee D., Bobbink I., Groot K., Sikking I., Raley J., Colban M., Smerud K., Trygg N., Waagaard E., Westad H., Rotkegel S., Spiechowicz U., Domoradzka M., Gawlowska M., Flygar A., Odmark I., Pettersson A., Blackwood S., Barclay J., Benham J., Brown R., Cureton L., Jackson D., Kennedy I., Leaper C., Taylor A., Winter C., Wise C., Nash M., Taylor Bennett A., Donaldson D., Chalmers K., Corderoy H., Bartkoske M., Bjerk C., Camarena A., Herskovitz L., Heuer C., Levin J., Robinson R., Wicklund B., Bentzel D., Cohen S., Costa C., Scranton R., Auwardt R., Boyer M., Cogdell P., Menahem S., Sheldrake J., Mount P., Fraenkel M., Bisscheroux P., Dempester J., Gleeson P., Harris G., Holmes C., Hyett K., Linton A., Miach P., Booth D., Druce L., Mantha M., Borg E., Green S., Killen J., Lynch Y., Colquhoun D., Herzig K., Row G., Addison J., Asa J., Beatson G., Calvird D., Edmunds J., Ferreira-Jardim A., Gwynne A., Mackay D., McLoughlin L., Wightwick C., Williams L., Ferrari P., Barry J., Hodson S., Zakrzewska W., Meagher E., Mulcahy M., Parnham A., Carney S., Garvey L., Gillies A., Hayes S., Mathew M., Fassett R., Anderson L., Clingeleffer C., Curnock A., Mayne L., Richardson D., Smith M., Smith S., Suranyi M., Howlin K., Chow J., Cleland B., Rayment G., Spicer T., Wong J., Wong M., Packham D., Alison C., Fraser I., Mitchell J., Nagle J., Brown F., Ellery C., Monkhouse J., Nandkumar J., Reith-Myers L., Gray N., Cocks C., Courtney M., Hollett P., Johnston C., Larsen H., Pollock A., Stewart S., Styles G., Wyndham R., Fanning M., Gibson W., Jackson S., Mannering M., Mercado E., Oliphant R., Sud K., Ubera N., Wood C., Karrasch J., Brinkley T., Estensen K., Moroney A., Sutton J., Warren R., Saltissi D., Jahke H., Roach H., Saltissi J., Wiederroth O'Brien M., Johnson D., Bali V., Evans M., Franzen K., Halbish S., Helyar J., Martin A., Mudge D., Sonnenburg K., Sudak J., Roger S., Almeida S., Andrews H., Bohringer L., Bouwhuis L., Brady L., Carpenter A., Warren S., Elias T., Bannister K., Chew G., Clarke J., Faull R., Hooper A., Jeffs L., Napier A., Peh C., Pirone K., Skilton F., Ranganathan D., Best J., Hart L., Healy H., Morgan C., Ratanjee S., Salisbury A., Jose M., Freeman J., Hamilton R., Kirkland G., Read G., Anderson H., Boekel K., Farrell M., Foreman A., Iliev K., Pedagogos E., Raspudic T., Pollock C., Cooper B., Kesselhut J., Macadam C., Pearse J., Rowland C., Tully H., Irish A., Dogra G., Coutts P., Hayes L., Khoo D., Nathoo B., Shakespeare K., Warger A., Gillin A., Burman J., George C., Sherwood S., Snelling P., Stevens C., Hutchison B., Luxton G., Devenny N., Herson H., Pellicano S., Kelly J., Coutelas J., Garlinge C., McClelland A., Pirabhahar S., Saleh H., Langham R., Englebright B., Giang M., Lanteri M., Mullins K., Turner C., Collett P., Stokoe S., Sutherland K., Talafua D., Talaulikar G., Clarkson A., Rees C., Carney G., Falk M., Gracey D., Jadeer A., Johnson P., Karpe K., Singer R., Walters G., McDonald S., Burgess J., Fischer K., Gentgall M., Hockley M., Veitch D., De Jersey P., Gillam A., Hartig V., Holland K., McArdle J., Washington W., Rangan G., Mikaheal M., Murie P., Perez N., Punnoose N., Smolonogov T., Taler N., Williams G., Wen C., Kohlhagen J., Wessels J., Johnson S., Reid A., Ryan J., Taprell D., Auinger M., Eigner M., Kodras K., Leithner C., Magpantay L., Marterer C., Prager R., Prinz C., Seiringer E., Kramar R., Mitter E., Stummvoll H., Dieplinger G., Wenzel R., Stolz G., Drose S., Edlinger E., Headlam-Leitner E., Miska H., Then M., Weninger S., Lhotta K., Neyer U., Dickie H., Smodek S., Sprenger-Mahr H., Rosenkranz A., Zitt E., Mayr B., Schinner A., Soltys G., Begin V., Brunet S., Cournoyer S., Gelinas M., Giroux C., Martineau J., Roy M., Savoie L., Agharazii M., Blouin J., Desmeules S., Langlois S., Samson F., Wong G., Constantini L., Jing J., Malko J., Rivers C., Rochester D., Skilling C., Wadgymar A., Wu G., Kates D., Husch J., Mantle M., Turri L., Barrett B., Curtis B., Greeley B., Hannaford M., Harnett J., Kelly M., Langille E., Morgan J., Murphy S., Karim M., Arbo T., Carpenito G., Chan V., DaRoza G., Friesen M., Kraus D., Lam S., Lange B., Minhas S., Starko R., Torng S., Vela K., Madore F., Roy P., Troyanov S., Bonnardeaux A., Lauzon L., Pichette V., Yeates K., Mahoney K., Myers C., Pilkey R., Moist L., Edgar M., House A., Kortas C., Mindorff S., Tam P., Chow S., Fung J., Nagai G., Ng P., Sikaneta T., Ting R., Forzley B., Clouatre Y., Cooper S., DaCosta H., Granger S., Valley S., Karunakaran S., Abdulhadi M., Altwasser C., Anderson S., Bergquist L., Wijeyesinghe C., Berst L., Horgan K., Coles K., Lotter T., Robson L., Barre P., Golden J., Golden M., Tanguay N., Rigatto C., Armstrong S., Fine A., Fontaine B., Friesen D., Henry S., Kraushar M., Reslerova M., Verrelli M., Rabbat C., Clase C., Suva G., Winegard N., Goldstein M., Curvelo S., Donnelly S., Huckle J., Marticorena R., Chan-Yan C., Chiu A., DeLuca L., Flamer D., Gill J., Jamal A., Jung B., Kiaii M., Landsberg D., Rozen N., Taylor P., Werb R., Pylypchuk G., Ahmed A., Barton J., Hundseth M., Kappel J., Keindel I., Klassen J., Pylypchuk S., Rindall M., Tobe S., Naimark D., Agelopoulos M., Chessman M., Hladunewich M., Perkins N., Sainsbury S., McCready W., Adams B., Tonelli M., Caldwell S., Kumar U., McMahon A., Nikitin S., Restall J., Treit S., Wysocki Y., Duncan J., Copland M., Jastrzebski J., Keown P., Kwan S., Rogers D., Shapiro J., Singh S., Sioson L., Yee K., Yeung C., Zacharias J., Bueti J., Dizon B., Lam H., Miller L., Ross M., Zarrillo M., Li Z., Wang C., Liu L., Hong M., Zheng H., Zuo W., Ge Z., Liu Q., Li Y., Sun K., Zhao R., Sun G., Wang F., Cui Z., Lou F., Du Y., Song L., Huang H., Song Z., Wang J., Zhou L., Wu R., Xiao R., Zhang Q., Duan N., Ju N., Wang A., Xu Z., Lu Z., Zhang Y., Zhao L., Zhang C., Mo Z., Xie Y., Xiong J., Chen J., Guo L., Zhao S., Peiskerova M., Jancova E., Kazderova M., Kobrova L., Gorun P., Kmentova T., Burgelova M., Lyerova L., Viklicky O., Berdych M., Nydlova Z., Jelinkova G., Moltas J., Pauzar T., Knetl P., Cahova J., Simkova J., Zakova M., Vankova S., Safarova R., Hruby M., Karlova R., Prikaska V., Sellenberg P., Vesela E., Malanova L., Vlasak J., Kaprova P., Novakova D., Kotherova K., Studenovska M., Christensen J., Solling J., Jepsen M., Kristensen V., Aerenlund H., Braemer-Jensen M., Kamper A., Raaschou S., Heaf J., Dreyer J., Freese P., Holm M., Munch M., Gade-Rasmussen E., Bredmose K., Daugaard H., Nielsen J., Friedberg M., Jensen D., Munk Plum M., Solling K., Dieperink H., Arp Nielsen L., Friborg E., Gloe-Jakobsen A., Thye Ronn P., Rasmussen K., Andersen C., Johansen A., Odum L., Ostergaard O., Pedersen L., Lykkegaard S., Aundal M., Faureholm Huess S., Danielsen H., Madsen J., Nyvang M., Ekstrand A., Boman H., Hartman J., Lipponen A., Lithovius R., Rauta V., Salmela A., Saloranta K., Forslund T., Koskiaho P., Jaaskelainen K., Kanninen M., Laine K., Asola M., Huhti J., Pentti M., Metsarinne K., Heiro M., Koivuviita N., Saarinen M., Tertti R., Choukroun G., Fournier A., Ducloux D., Marechal F., Simula Faivre D., Combe C., Douillet M., Lamblot T., Nardi H., Vendrely B., Bourbigot B., Ferlandin S., Zaoui P., Jouet C., Geffroy-Guiberteau S., Bugnazet L., Aldigier J., El Hamel-Belili C., Giraud S., Dussol B., Berland Y., Chollet M., Sichez H., Cristol J., Canaud B., Morena M., Rodriguez A., Kessler M., Mizejewski B., Risse B., Urena Torres P., Bou-Bekr M.A., Arezki C., Ras El Qdim P., Vela C., Borsato F., Talairach A., Normand M., Normand V., Rieu P., Gauthier B., Vigneron-Foy C., Wolak A., Menoyo V., Alos L., Caillette-Beaudoin A., Berger V., Al-Sarraf S., Konnerth I., Urban C., Weiner S., Boesken W., Jochum E., Kiefer C., Wagner A., Krumme B., Bohler J., Bonow B., Hohenstatt U., Mettang T., Rockel A., Langanke J., Lipponer H., Dunschen-Weimar G., Dunst R., Hubel E., Petrik R., Rengel R., Schmidgen M., Mayr H., Garschhammer C., Weirauch S., Anger H., Goock T., Mai A., Bast I., Suptitz C., Iwig B., Florschutz K., Hasselbacher R., Sauerbrey G., Delrieux S., Rau S., Poley M., Laux R., Schonfelder O., Kunowski G., Fuchs G., Hoffmann K., Schurger R., Brensing K., Guven Z., Immenkamp C., Kottmann C., Schmitt H., Schulz M., Arnold P., Knaup R., Schneider H., Siemsen H., Pyriki P., Korkemeyer F., Pyriki R., Siebrecht A., Schulz E., Krumwiede A., Kruse D., Lucke S., Keim H., Fink H., Fischer S., Klingbeil A., Kuhlmei K., Ortwein-Horn N., Merker L., Bayer B., Benamar K., Emmert S., Floten E., Holzheuer K., Lummer M., Ossendorf E., Scholz M., Oppitz M., Georgiew L., Tripps C., Wendehake M., Lange D., Pingel V., Brause M., Schanze W., Duygulu E., Dellanna F., Heinemann-Nieberding S., Sturmer C., Wieczorek K., Zarga O., Kullmer B., Kullmer S., Akin M., Gondolf M., Schutterle S., Walker G., Bertsch R., Seul M., Allendorff J., Siehler R., Stemmler S., Baldus M., Adler A., Harter S., Wurmell W., Moller M., Hame C., Muller M., Schreiber M., Schurfeld C., Millington-Herrmann M., Benschneider A., Gaffal J., Sprunken U., Bohling M., Wunderlich S., Schramm L., Kollenbrath C., Netzer K., Sieber T., Zimmermann J., Bellersen M., Uerkvitz M., David-Walek T., Hauschildt B., Leimenstoll G., Lonnemann G., Hilfenhaus M., Benedetto C., Stockmann S., Ichtiaris P., Jungmann A., Neumeier K., Stoof A., Bohmer K., Kirpal A., Knogl A., Flege F., Franke K., Groth P., Parensen E., Bockmann M., Przyklenk P., Piazolo L., Thinius-Jaudas L., Versen A., Hettich R., Arendt R., Geiger K., Hoppe H., Schwarting A., Beyer T., Faust J., Hazenbiller A., Tschirner S., Grupp C., Dorsch O., Eigner-Schmidtchen M., Michler K., Roth J., Schramm S., Waldmuller G., Riedl B., Vogele-Dirks H., Linz J., Biggar P., Hennemann H., Bauer G., Buchholz J., Fischer P., Bihlmaier W., Baumann A., Peichl B., Roser S., Ludewig S., Ricksgers M., Szendzielorz M., Baus A., Baust K., Schaller P., Schnellbacher G., Sorensen S., Buschges-Seraphin B., Hauenstein L., Hofmann B., Nikolay J., Merkel F., Nebel M., Petersen J., Schweb S., Zeissler H., Baumhackel K., Krauss A., Schafer R., Pastor A., Zielinski B., Strauss H., Theis H., Burkhardt K., Heckel M., Hussendorfer K., Bahner U., Brandl M., Hammerl-Kraus B., Herrmann D., Kramer H., Baudenbacher H., Blaser C., Buschmann G., Eckert G., Ehrich H., Hofmann K., Huller U., Geiger H., Becker B., Hoischen S., Bartel C., Hennig J., Obermuller N., Schulte C., Fischereder M., Burchardi F., Rupprecht H., Weidner S., Anders H., Andriaccio L., Lederer S., Ricken G., Strasser C., Lammert A., Schmitt W., Van Der Woude F., Langhauser B., Markau S., Osten B., Thiemicke D., Dorligschaw O., Weickert M., Breunig F., Denninger G., Osiek S., Rebstock W., Schulz P., Swoboda F., De Cicco D., Harlos J., Lebert A., Riegel M., Schmiedeke T., Hoffmann U., Nolle M., Jankrift P., Pfleiderer H., Witta J., Wittler B., Luth J., Dumann H., Habel U., Torp A., Sehland D., Tiess M., Etzold C., Friederiszik A., Morgenroth A., Dybala A., Suffel A., Leimbach T., Kron J., Sauer S., Meyer T., Meyer M., Lammers U., Bekman J., Holtz S., Kausler-Book B., Stobbe S., Hohage H., Heck M., Schulte F., Welling U., Zeh M., Seyfried J., De Heij T., Menzinger A., Weinreich T., Hopf M., Groll J., Kammholz K., Peters K., Schwietzer G., Kreft B., Weibchen U., Vosskuhler A., Hollenbeck M., Klaue K., Rzepucha E., Sperling K., Seeger W., Weyer J., Heine C., Kirste P., Zemann B., Alscher D., Rumpf D., Wullen B., Bengel A., Friedrich B., Kirschner T., Knodler U., Machleidt C., Niederstrasser K., Noack E., Wilhelm J., Heuer H., Dulea J., Piolot R., Rudke M., Treinen G., Elberg B., Hanke J., Nitschke T., Rosendahl C., Schmitz A., Schrader J., Kulschewski A., Lubcke C., Hammersen F., Luders S., Venneklaas U., Muhlfeld A., Arabi Al-Khanne F., Ketteler M., Politt D., Schuster C., Eitner F., Goretz U., Heidenreich S., Janssen U., Kranz A., Moormann E., Schneider B., Weber W., Frei U., Jovanovic T., Asmus H., Canaan-Kuhl S., Pannier L., Petersen S., Pluer M., Schaeffner E., Schafer C., Warncke S., Schmieder R., Donhauser C., Schulze B., Koziolek M., Bechtel W., Kurz B., Strutz F., Bramlage C., Dreyer S., Mommeyer E., Niemann J., Scheel A., Troche-Polzien I., Weber F., Heine G., Girndt M., Lizzi F., Rogacev K., Lindner T., Achenbach H., Peschel K., Beige J., Jentho S., Kreyssig C., Prill K., Renders L., Walcher J., Cerny S., Fulbier A., Kristen H., Nitschke M., Kramer J., Marek P., Meier M., Schlieter J., Heyne N., Bachmann F., Faber M., Klipp K., Kustner U., Risler T., Rath T., Ruf T., Budiman D., Seidel C., Weik S., Teo S.M., Lee L.Y., Azizah H., Faridunishah S.A., Foo S.M., Go K.W., Ghazali A., Koh K.H., Zaki M., Wong H.S., Bavanandan S., Boey L.M., Lily M., Wong S.L., Rosnawati Y., Zawawi N., Azimawati A., Hindun A., Hasnah J., Korina R., Yunaidah A., Noraidah P., Ong L.M., Noor Asma A., Liew Y.F., Rozina G., Cheong Y.H., Ang A.H., Dayang J., Lim L.S., Sukeri M., Ramli S., Zulkifli M., Wan Mahmood W.K., Goh B.L., Sarifah B., Bee B.C., Ramasamy C., Ruszarimah S., Liu W.J., Razali O., Haslinah S., Vaithilingam I., Jaaini A., Faridah L., Ng K.H., Krishnan P., Rosnah A.A., Nor Azizah A.S., Tam C.C., Tan S.H., Tan C.C., Shahnaz F.K., Wazir H., Munusamy P., Wan Shaariah M.Y., Chew T.F., Fuziah Z., Tan C.H.H., Maria L., Javelin P., Lim S.K., Nazatul S.B., Engkasan L.P., Tan S.Y., Wong M.G., Julita A.A., Ang B.B., Krishnan S., Seet W.W.T., Liew S.K., Keng T.C., Tobe T., Deelen M., Klaassen I., Grave W., Emmen M., Janssen W., Bossen W., Elzinga B., Van Der Velden A., Hemmelder M., Slagman M., Waanders F., Viergever P., Boerema I., Potter Van Loon B., Muthert B., Geers T., Schollaert N., Van Weverwijk I., Veen P., Woittiez A., Krikken J., Kwakernaak A., Visser F., Navis G., Hoekstra F., Hawkins S., McGregor D., Usher J., MacGinley R., Schollum J., Ellis G., Voss D., Rosman J., Upjohn M., Panlilio N., Madhan K., Naicker V., Anderson E., Bushell M., Lumb N., Pepperell B., Sizeland P., Hayett S., Sullivan N., Tuffery C., Macdonald A., Ostapowicz T., Wessel-Aas T., Wessel-Aas H., Bjorbaek E., Bjorbaek R., Simso I., Oien C., Bergrem H., Espedal S., Kronborg J., Solbakken K., Rocke J., Aakervik O., Haugen V., Eide T., Berglund J., Loland W., Schei T., Stromsaether C., Willadsen H., Lyngdal P., Vad A., Waldum B., Froslid G., Roaldsnes C., Rustad D., Soderblom P., Eriksen B., Hanssen E., Julsrud J., Mathisen U., Pedersen M., Rumsfeld M., Toft I., Berget K., Landsverk K., Tveiten G., Wamstad H., Klinger M., Krajewska M., Golebiowski T., Kusztal M., Spiechowicz-Zaton U., Rutkowski B., Renke M., Tylicki L., Czekalski S., Koziol L., Wanic-Kossowska M., Wasik-Olejnik A., Nowicki M., Dryja P., Kurnatowska I., Zawiasa A., Ciszek M., Gomolka M., Mysliwiec M., Brzosko S., Mazerska M., Hruby Z., Koscielniak K., Stanek-Piotrowska M., Mesjasz J., Rudka R., Baranski M., Jupowiecki J., Klein D., Switalski M., Kuriga M., Ostrowski M., Lidman A., Linde T., Waltersson K., Weiss L., Andersson G., Lindell C., Welander G., Jacobson S., Edensjo P., Wallin J., Linder M., Karsberg M., Hellgren K., Lonn I., Frisenette-Fich C., Johansson A., Lundstrom A., Mauritz N., Stahl-Nilsson A., Tobafard N., Hellberg O., Ejemar E., Von Schmalensee N., Gunne T., Eriksson A., Ostberg S., Svensson C., Mulec H., Jacobsson A., Karlsson M., Onnermalm L., Osagie S., Ekengren U., Larsson M., Lindberger K., Olofsson A., Samuelsson O., Beagan L., Dezfoolian H., Just M., Ortegren L., Saeed A., Strand U., Ramsauer B., Hultstrom D., Nordlinder K., Sundberg I., Oqvist B., Green C., Fernstrom A., Cassel A., Goransson I., Gylling M., Jorgensen A., Sterner G., Christensson A., Hjelmstedt P., Nystrom A., Sundin P., Samuelsson I., Tidman M., Johansson M., Lofgren Andersson M., Ohman M., Andersson P., Hallberg Karlsson A., Ringstad L., Chittinandana A., Chailimpamontree W., Gojaseni P., Singprasert R., Tungsanga K., Amphun W., Intim P., Kanjanabuch T., Poowarattanakul D., Treratha C., Wongvan P., Jittikanont S., Suriya T., Indrasthitya P., Sumethkul V., Ingsathit A., Jansomwong J., Lertchalorarn K., Phachiyanukul V., Phiromkit T., Saengsri S., Vareesangthip K., Chawanasuntorapoj R., Kiattisunthorn K., Larpkitkachorn R., Webster J., Henderson J., Jayne D., Hollis J., Townsend K., Harron C., Bleakley N., Hanley N., Morgan S., Brittney L., Brown H., Maxwell P., Murtagh H., Thomas M., Burke E., Carmody M., Cox G., 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Mitra S., Woolfson R., Yang R., Williams A., Richards K., Turner A., Odum J., Rylance P., Smallwood A., Ward J., Henderson I., McMahon M., Ross C., Burrows M., Morais J., Rajan S., Tindall H., Barrett C., Kelly F., El-Nahas M., Bartholomew J., Edwards L., Okhuoya F., Bebb C., Cassidy M., Brand S., Quashie-Howard M., Taggart C., Capps N., Tonks L., Mason J., Powell S., Watkins L., Ball S., Dutton M., Fifer L., McGlynn F., Wood M., Jenkins D., Allan N., Fahal I., Elhag-Ali H., King J., Peel R., Potts L., Logie I., McGhie F., Naik R., Parry R., Andain K., Durkin S., D'Souza R., Harrison D., Cooke J., Kinyanjui R., Harper J., Algate K., McCarthy M., Van Eker D., Thuraisingham R., Chinodya M., Deelchand V., Garcia R., Ngango R., Rolfe C., Williams K., Solomon L., Heap T., MacDowall P., Saunderson Smith L., MacDiarmaid-Gordon A., Harman W., Smithson H., Robertson D., Gammon B., O'Grady D., Verow C., Rogerson M., Berry L., Gough C., Hayward E., Jones C., Payne T., Rowe L., Sibley C., Szymanski J., Almond M., Bourton L., Bromwich C., Dawson S., Mason S., Oliveira D., Ramkhelawon R., Tuazon J., Andrews P., Archer K., Moore A., Thomas G., Velazquez C., Mumtaz R., Roberts R., Farquhar F., Ott J., Fenwick S., Callaway A., Garrett P., Dees L., McDonagh U., Garner S., Zehnder D., Aldridge N., Dyer C., Gomez M., Hewins S., McCarthy K., Rush J., Spencer S., Harvey M., Mills H., Drew P., Henry M., Wilberforce S., Worth D., Adair Z., Hartley J., Jibani M., Jones D., Swan S., Shamp T., Alcorn H., Bookey J., Cannon C., Jarvis K., Muesing C., Murphy M., Muster H., Planting M., Strand C., Middleton J., Gitter K., Mace N., Schumm D., Pogue V., Alimohammadi B., Arora P., Herbert L., Cheng J., Dowie D., Mohan S., Peters G., Tuttle K., Albritton S., Benedetti R., Joshi S., Lund B., Shuler L., Trevino M., Mai K., Osborn T., Parekh R., Eustace J., Novak G., Patterson S., Lindsey C., Hill T., Liston M., Wiegmann T., Nagaria A., Hurd C., Hurst A., Omoscharka E., Parks S., Price V., Reaich R., Schouten D., Rashid H., Birtcher K., Cantu J., Tait C., Taun W., Fadem S., Das D., Khosla U., Brown C., Brown T., Buquing J., Cromwell H., Dickson N., Najimipour B., Robeson J., Tabibi W., Mulloy L., Bailey K., Burton B., Fall P., Jagadeesan M., Paulson W., Szerlip H., White J., Faulkner M., Adeleye O., Boatright D., Mensah D., Nwankwo U., Crutcher L., Cummings C., Floyd M., Putatunda B., Ross J., Sanford V., Thadani U., Haragsim L., Parker B., Rogan L., Thresher M., Turner J., Dworkin L., Mignano D., O'Mara A., Shemin D., Bakris G., Basta E., Chua D., Neri G., Ahmed I., Elliott W., Fondren L., Hasabou N., Khosla N., Mazin A., Riehle J., Kovesdy C., Mendoza J., Ahmadzadeh S., Iranmanesh A., Lewis M., Lu J., Benabe J., Gonzalez-Melendez E., Padilla B., Serrano J., Russ T., Athmann L., Funke L., Larson P., Roach D., Salveson B., Nogueira J., Hanes D., Hise M., Light P., Copland E., Fink J., Hakim M., Hough K., McMinn S., Weir M., Young C., Kershaw G., Hill I., White B., Plumb T., Florescu M., Groggel G., Martin M., Rao V., Denu-Ciocca C., Candiani C., Cooper J., Gordon B., Joy M., Kiser M., Lambeth C., Rosas S., Cochetti P., Robinson J., Schankel K., Teng H., Weise W., Geneidy A., Murray P., Solomon R., De Waal D., LaPointe S., Schoenknecht A., Campese V., Habashy M., Ananthakrisna R., Bedwani D., Fazli U., Fetrat M., Frampton Q., Kaldas B., Kazarian V., Pitts L., Sadeghi A., Yeasmin N., Young E., Fissell R., Belanger K., Ricci N., Farwell W., Bowman T., Dhingra R., Pesenson A., Ambrosino J., Chittamooru S., Kaufman J., Ramos M., Yap C., Nakhle S., Aligaen L., Duren D., Laine B., Moore S., Tuazon H., Coyne D., Audrain J., Bryant B., Dombek S., Freeman S., Klein P., Germain M., Berkowitz A., Bokhari A., Braden G., Diaz A., Greco B., Mulhern J., O'Shea M., Poindexter A., Poppel D., Ryan M., Sweet S., Ye J., Osterman J., Lin T., Mays B., Rizvi A., Sonnier C., Twining C., Wang S., Hix M., Schenck J., Baigent C., Landray M., Reith C., Dasgupta T., Emberson J., Herrington W., Lewis D., Mafham M., Collins R., Bray C., Chen Y., Baxter A., Young A., Hill M., Knott C., Cass A., Feldt-Rasmussen B., Fellstrom B., Grobbee R., Gronhagen-Riska C., Haas M., Holdaas H., Hooi L.S., Jiang L., Kasiske B., Krairittichai U., Levin A., Massy Z., Tesar V., Walker R., Wanner C., Wheeler D., Wiecek A., Majoni W., Simpson D., Strony J., Musliner T., Agodoa L., Armitage J., Chen Z., Craig J., De Zeeuw D., Gaziano M., Grimm R., Krane V., Neal B., Ophascharoensuk V., Pedersen T., Sleight P., Tobert J., Tomson C., Sandercock P., Keech A., Whelton P., Yusuf S., Peto R., Parish S., Dolph L., Bahu T., Booth-Davey E., Brewster A., Yau F., Denis E., Frederick K., Haywood D., Heineman J., Howard S., Jayne K., Madgwick Z., Michell S., Murphy K., Ning L., Nolan J., Nunn M., Roberts J., Wickman M., Bowman L., Bulbulia R., Haynes R., Rahimi K., Rahman N., Ait-Sadi R., Barton I., Zhu W., Clark S., Kourellias K., Radley M., Brown K., Worthing D., Coates G., Goodenough B., Lucas N., Carreras A., Currie R., Donaldson O., Fjalling E., Gallagher M., Gibson K., Goddard J., Healy J., Hones L., Jardine M., Kwong I., Merai M., Murray S., Perkovic V., Rendina A., Gallo K., Caron S., Carlson K., Foley K., Matzek S., Mewhort L., O'Donoghue S., Perel-Winkler A., Terins T., Nie Q., Yu H., Ge L., Hao D., Li L., Pang X., Wei X., Yan G., Certikova Chabova V., Holst H., Molvadgaard T., Munksgaard D., Peltonen Y., Liabeuf S., Lebel C., Ouabou L., Bauer B., Bergmann K., Beusch M., Cavitt D., Drechsler C., Dulau I., Hugen K., Kempf S., Kuchenmeister B., Pscheidl V., Schmiedeke D., Schwarz M., Speerschneider K., Stahl B., Lim B.C., Nadia H., Zishareena M.F., Vasuthavan S., Ganesapillai A.T., Yuen S., Grobbee D., Bobbink I., Groot K., Sikking I., Raley J., Colban M., Smerud K., Trygg N., Waagaard E., Westad H., Rotkegel S., Spiechowicz U., Domoradzka M., Gawlowska M., Flygar A., Odmark I., Pettersson A., Blackwood S., Barclay J., Benham J., Brown R., Cureton L., Jackson D., Kennedy I., Leaper C., Taylor A., Winter C., Wise C., Nash M., Taylor Bennett A., Donaldson D., Chalmers K., Corderoy H., Bartkoske M., Bjerk C., Camarena A., Herskovitz L., Heuer C., Levin J., Robinson R., Wicklund B., Bentzel D., Cohen S., Costa C., Scranton R., Auwardt R., Boyer M., Cogdell P., Menahem S., Sheldrake J., Mount P., Fraenkel M., Bisscheroux P., Dempester J., Gleeson P., Harris G., Holmes C., Hyett K., Linton A., Miach P., Booth D., Druce L., Mantha M., Borg E., Green S., Killen J., Lynch Y., Colquhoun D., Herzig K., Row G., Addison J., Asa J., Beatson G., Calvird D., Edmunds J., Ferreira-Jardim A., Gwynne A., Mackay D., McLoughlin L., Wightwick C., Williams L., Ferrari P., Barry J., Hodson S., Zakrzewska W., Meagher E., Mulcahy M., Parnham A., Carney S., Garvey L., Gillies A., Hayes S., Mathew M., Fassett R., Anderson L., Clingeleffer C., Curnock A., Mayne L., Richardson D., Smith M., Smith S., Suranyi M., Howlin K., Chow J., Cleland B., Rayment G., Spicer T., Wong J., Wong M., Packham D., Alison C., Fraser I., Mitchell J., Nagle J., Brown F., Ellery C., Monkhouse J., Nandkumar J., Reith-Myers L., Gray N., Cocks C., Courtney M., Hollett P., Johnston C., Larsen H., Pollock A., Stewart S., Styles G., Wyndham R., Fanning M., Gibson W., Jackson S., Mannering M., Mercado E., Oliphant R., Sud K., Ubera N., Wood C., Karrasch J., Brinkley T., Estensen K., Moroney A., Sutton J., Warren R., Saltissi D., Jahke H., Roach H., Saltissi J., Wiederroth O'Brien M., Johnson D., Bali V., Evans M., Franzen K., Halbish S., Helyar J., Martin A., Mudge D., Sonnenburg K., Sudak J., Roger S., Almeida S., Andrews H., Bohringer L., Bouwhuis L., Brady L., Carpenter A., Warren S., Elias T., Bannister K., Chew G., Clarke J., Faull R., Hooper A., Jeffs L., Napier A., Peh C., Pirone K., Skilton F., Ranganathan D., Best J., Hart L., Healy H., Morgan C., Ratanjee S., Salisbury A., Jose M., Freeman J., Hamilton R., Kirkland G., Read G., Anderson H., Boekel K., Farrell M., Foreman A., Iliev K., Pedagogos E., Raspudic T., Pollock C., Cooper B., Kesselhut J., Macadam C., Pearse J., Rowland C., Tully H., Irish A., Dogra G., Coutts P., Hayes L., Khoo D., Nathoo B., Shakespeare K., Warger A., Gillin A., Burman J., George C., Sherwood S., Snelling P., Stevens C., Hutchison B., Luxton G., Devenny N., Herson H., Pellicano S., Kelly J., Coutelas J., Garlinge C., McClelland A., Pirabhahar S., Saleh H., Langham R., Englebright B., Giang M., Lanteri M., Mullins K., Turner C., Collett P., Stokoe S., Sutherland K., Talafua D., Talaulikar G., Clarkson A., Rees C., Carney G., Falk M., Gracey D., Jadeer A., Johnson P., Karpe K., Singer R., Walters G., McDonald S., Burgess J., Fischer K., Gentgall M., Hockley M., Veitch D., De Jersey P., Gillam A., Hartig V., Holland K., McArdle J., Washington W., Rangan G., Mikaheal M., Murie P., Perez N., Punnoose N., Smolonogov T., Taler N., Williams G., Wen C., Kohlhagen J., Wessels J., Johnson S., Reid A., Ryan J., Taprell D., Auinger M., Eigner M., Kodras K., Leithner C., Magpantay L., Marterer C., Prager R., Prinz C., Seiringer E., Kramar R., Mitter E., Stummvoll H., Dieplinger G., Wenzel R., Stolz G., Drose S., Edlinger E., Headlam-Leitner E., Miska H., Then M., Weninger S., Lhotta K., Neyer U., Dickie H., Smodek S., Sprenger-Mahr H., Rosenkranz A., Zitt E., Mayr B., Schinner A., Soltys G., Begin V., Brunet S., Cournoyer S., Gelinas M., Giroux C., Martineau J., Roy M., Savoie L., Agharazii M., Blouin J., Desmeules S., Langlois S., Samson F., Wong G., Constantini L., Jing J., Malko J., Rivers C., Rochester D., Skilling C., Wadgymar A., Wu G., Kates D., Husch J., Mantle M., Turri L., Barrett B., Curtis B., Greeley B., Hannaford M., Harnett J., Kelly M., Langille E., Morgan J., Murphy S., Karim M., Arbo T., Carpenito G., Chan V., DaRoza G., Friesen M., Kraus D., Lam S., Lange B., Minhas S., Starko R., Torng S., Vela K., Madore F., Roy P., Troyanov S., Bonnardeaux A., Lauzon L., Pichette V., Yeates K., Mahoney K., Myers C., Pilkey R., Moist L., Edgar M., House A., Kortas C., Mindorff S., Tam P., Chow S., Fung J., Nagai G., Ng P., Sikaneta T., Ting R., Forzley B., Clouatre Y., Cooper S., DaCosta H., Granger S., Valley S., Karunakaran S., Abdulhadi M., Altwasser C., Anderson S., Bergquist L., Wijeyesinghe C., Berst L., Horgan K., Coles K., Lotter T., Robson L., Barre P., Golden J., Golden M., Tanguay N., Rigatto C., Armstrong S., Fine A., Fontaine B., Friesen D., Henry S., Kraushar M., Reslerova M., Verrelli M., Rabbat C., Clase C., Suva G., Winegard N., Goldstein M., Curvelo S., Donnelly S., Huckle J., Marticorena R., Chan-Yan C., Chiu A., DeLuca L., Flamer D., Gill J., Jamal A., Jung B., Kiaii M., Landsberg D., Rozen N., Taylor P., Werb R., Pylypchuk G., Ahmed A., Barton J., Hundseth M., Kappel J., Keindel I., Klassen J., Pylypchuk S., Rindall M., Tobe S., Naimark D., Agelopoulos M., Chessman M., Hladunewich M., Perkins N., Sainsbury S., McCready W., Adams B., Tonelli M., Caldwell S., Kumar U., McMahon A., Nikitin S., Restall J., Treit S., Wysocki Y., Duncan J., Copland M., Jastrzebski J., Keown P., Kwan S., Rogers D., Shapiro J., Singh S., Sioson L., Yee K., Yeung C., Zacharias J., Bueti J., Dizon B., Lam H., Miller L., Ross M., Zarrillo M., Li Z., Wang C., Liu L., Hong M., Zheng H., Zuo W., Ge Z., Liu Q., Li Y., Sun K., Zhao R., Sun G., Wang F., Cui Z., Lou F., Du Y., Song L., Huang H., Song Z., Wang J., Zhou L., Wu R., Xiao R., Zhang Q., Duan N., Ju N., Wang A., Xu Z., Lu Z., Zhang Y., Zhao L., Zhang C., Mo Z., Xie Y., Xiong J., Chen J., Guo L., Zhao S., Peiskerova M., Jancova E., Kazderova M., Kobrova L., Gorun P., Kmentova T., Burgelova M., Lyerova L., Viklicky O., Berdych M., Nydlova Z., Jelinkova G., Moltas J., Pauzar T., Knetl P., Cahova J., Simkova J., Zakova M., Vankova S., Safarova R., Hruby M., Karlova R., Prikaska V., Sellenberg P., Vesela E., Malanova L., Vlasak J., Kaprova P., Novakova D., Kotherova K., Studenovska M., Christensen J., Solling J., Jepsen M., Kristensen V., Aerenlund H., Braemer-Jensen M., Kamper A., Raaschou S., Heaf J., Dreyer J., Freese P., Holm M., Munch M., Gade-Rasmussen E., Bredmose K., Daugaard H., Nielsen J., Friedberg M., Jensen D., Munk Plum M., Solling K., Dieperink H., Arp Nielsen L., Friborg E., Gloe-Jakobsen A., Thye Ronn P., Rasmussen K., Andersen C., Johansen A., Odum L., Ostergaard O., Pedersen L., Lykkegaard S., Aundal M., Faureholm Huess S., Danielsen H., Madsen J., Nyvang M., Ekstrand A., Boman H., Hartman J., Lipponen A., Lithovius R., Rauta V., Salmela A., Saloranta K., Forslund T., Koskiaho P., Jaaskelainen K., Kanninen M., Laine K., Asola M., Huhti J., Pentti M., Metsarinne K., Heiro M., Koivuviita N., Saarinen M., Tertti R., Choukroun G., Fournier A., Ducloux D., Marechal F., Simula Faivre D., Combe C., Douillet M., Lamblot T., Nardi H., Vendrely B., Bourbigot B., Ferlandin S., Zaoui P., Jouet C., Geffroy-Guiberteau S., Bugnazet L., Aldigier J., El Hamel-Belili C., Giraud S., Dussol B., Berland Y., Chollet M., Sichez H., Cristol J., Canaud B., Morena M., Rodriguez A., Kessler M., Mizejewski B., Risse B., Urena Torres P., Bou-Bekr M.A., Arezki C., Ras El Qdim P., Vela C., Borsato F., Talairach A., Normand M., Normand V., Rieu P., Gauthier B., Vigneron-Foy C., Wolak A., Menoyo V., Alos L., Caillette-Beaudoin A., Berger V., Al-Sarraf S., Konnerth I., Urban C., Weiner S., Boesken W., Jochum E., Kiefer C., Wagner A., Krumme B., Bohler J., Bonow B., Hohenstatt U., Mettang T., Rockel A., Langanke J., Lipponer H., Dunschen-Weimar G., Dunst R., Hubel E., Petrik R., Rengel R., Schmidgen M., Mayr H., Garschhammer C., Weirauch S., Anger H., Goock T., Mai A., Bast I., Suptitz C., Iwig B., Florschutz K., Hasselbacher R., Sauerbrey G., Delrieux S., Rau S., Poley M., Laux R., Schonfelder O., Kunowski G., Fuchs G., Hoffmann K., Schurger R., Brensing K., Guven Z., Immenkamp C., Kottmann C., Schmitt H., Schulz M., Arnold P., Knaup R., Schneider H., Siemsen H., Pyriki P., Korkemeyer F., Pyriki R., Siebrecht A., Schulz E., Krumwiede A., Kruse D., Lucke S., Keim H., Fink H., Fischer S., Klingbeil A., Kuhlmei K., Ortwein-Horn N., Merker L., Bayer B., Benamar K., Emmert S., Floten E., Holzheuer K., Lummer M., Ossendorf E., Scholz M., Oppitz M., Georgiew L., Tripps C., Wendehake M., Lange D., Pingel V., Brause M., Schanze W., Duygulu E., Dellanna F., Heinemann-Nieberding S., Sturmer C., Wieczorek K., Zarga O., Kullmer B., Kullmer S., Akin M., Gondolf M., Schutterle S., Walker G., Bertsch R., Seul M., Allendorff J., Siehler R., Stemmler S., Baldus M., Adler A., Harter S., Wurmell W., Moller M., Hame C., Muller M., Schreiber M., Schurfeld C., Millington-Herrmann M., Benschneider A., Gaffal J., Sprunken U., Bohling M., Wunderlich S., Schramm L., Kollenbrath C., Netzer K., Sieber T., Zimmermann J., Bellersen M., Uerkvitz M., David-Walek T., Hauschildt B., Leimenstoll G., Lonnemann G., Hilfenhaus M., Benedetto C., Stockmann S., Ichtiaris P., Jungmann A., Neumeier K., Stoof A., Bohmer K., Kirpal A., Knogl A., Flege F., Franke K., Groth P., Parensen E., Bockmann M., Przyklenk P., Piazolo L., Thinius-Jaudas L., Versen A., Hettich R., Arendt R., Geiger K., Hoppe H., Schwarting A., Beyer T., Faust J., Hazenbiller A., Tschirner S., Grupp C., Dorsch O., Eigner-Schmidtchen M., Michler K., Roth J., Schramm S., Waldmuller G., Riedl B., Vogele-Dirks H., Linz J., Biggar P., Hennemann H., Bauer G., Buchholz J., Fischer P., Bihlmaier W., Baumann A., Peichl B., Roser S., Ludewig S., Ricksgers M., Szendzielorz M., Baus A., Baust K., Schaller P., Schnellbacher G., Sorensen S., Buschges-Seraphin B., Hauenstein L., Hofmann B., Nikolay J., Merkel F., Nebel M., Petersen J., Schweb S., Zeissler H., Baumhackel K., Krauss A., Schafer R., Pastor A., Zielinski B., Strauss H., Theis H., Burkhardt K., Heckel M., Hussendorfer K., Bahner U., Brandl M., Hammerl-Kraus B., Herrmann D., Kramer H., Baudenbacher H., Blaser C., Buschmann G., Eckert G., Ehrich H., Hofmann K., Huller U., Geiger H., Becker B., Hoischen S., Bartel C., Hennig J., Obermuller N., Schulte C., Fischereder M., Burchardi F., Rupprecht H., Weidner S., Anders H., Andriaccio L., Lederer S., Ricken G., Strasser C., Lammert A., Schmitt W., Van Der Woude F., Langhauser B., Markau S., Osten B., Thiemicke D., Dorligschaw O., Weickert M., Breunig F., Denninger G., Osiek S., Rebstock W., Schulz P., Swoboda F., De Cicco D., Harlos J., Lebert A., Riegel M., Schmiedeke T., Hoffmann U., Nolle M., Jankrift P., Pfleiderer H., Witta J., Wittler B., Luth J., Dumann H., Habel U., Torp A., Sehland D., Tiess M., Etzold C., Friederiszik A., Morgenroth A., Dybala A., Suffel A., Leimbach T., Kron J., Sauer S., Meyer T., Meyer M., Lammers U., Bekman J., Holtz S., Kausler-Book B., Stobbe S., Hohage H., Heck M., Schulte F., Welling U., Zeh M., Seyfried J., De Heij T., Menzinger A., Weinreich T., Hopf M., Groll J., Kammholz K., Peters K., Schwietzer G., Kreft B., Weibchen U., Vosskuhler A., Hollenbeck M., Klaue K., Rzepucha E., Sperling K., Seeger W., Weyer J., Heine C., Kirste P., Zemann B., Alscher D., Rumpf D., Wullen B., Bengel A., Friedrich B., Kirschner T., Knodler U., Machleidt C., Niederstrasser K., Noack E., Wilhelm J., Heuer H., Dulea J., Piolot R., Rudke M., Treinen G., Elberg B., Hanke J., Nitschke T., Rosendahl C., Schmitz A., Schrader J., Kulschewski A., Lubcke C., Hammersen F., Luders S., Venneklaas U., Muhlfeld A., Arabi Al-Khanne F., Ketteler M., Politt D., Schuster C., Eitner F., Goretz U., Heidenreich S., Janssen U., Kranz A., Moormann E., Schneider B., Weber W., Frei U., Jovanovic T., Asmus H., Canaan-Kuhl S., Pannier L., Petersen S., Pluer M., Schaeffner E., Schafer C., Warncke S., Schmieder R., Donhauser C., Schulze B., Koziolek M., Bechtel W., Kurz B., Strutz F., Bramlage C., Dreyer S., Mommeyer E., Niemann J., Scheel A., Troche-Polzien I., Weber F., Heine G., Girndt M., Lizzi F., Rogacev K., Lindner T., Achenbach H., Peschel K., Beige J., Jentho S., Kreyssig C., Prill K., Renders L., Walcher J., Cerny S., Fulbier A., Kristen H., Nitschke M., Kramer J., Marek P., Meier M., Schlieter J., Heyne N., Bachmann F., Faber M., Klipp K., Kustner U., Risler T., Rath T., Ruf T., Budiman D., Seidel C., Weik S., Teo S.M., Lee L.Y., Azizah H., Faridunishah S.A., Foo S.M., Go K.W., Ghazali A., Koh K.H., Zaki M., Wong H.S., Bavanandan S., Boey L.M., Lily M., Wong S.L., Rosnawati Y., Zawawi N., Azimawati A., Hindun A., Hasnah J., Korina R., Yunaidah A., Noraidah P., Ong L.M., Noor Asma A., Liew Y.F., Rozina G., Cheong Y.H., Ang A.H., Dayang J., Lim L.S., Sukeri M., Ramli S., Zulkifli M., Wan Mahmood W.K., Goh B.L., Sarifah B., Bee B.C., Ramasamy C., Ruszarimah S., Liu W.J., Razali O., Haslinah S., Vaithilingam I., Jaaini A., Faridah L., Ng K.H., Krishnan P., Rosnah A.A., Nor Azizah A.S., Tam C.C., Tan S.H., Tan C.C., Shahnaz F.K., Wazir H., Munusamy P., Wan Shaariah M.Y., Chew T.F., Fuziah Z., Tan C.H.H., Maria L., Javelin P., Lim S.K., Nazatul S.B., Engkasan L.P., Tan S.Y., Wong M.G., Julita A.A., Ang B.B., Krishnan S., Seet W.W.T., Liew S.K., Keng T.C., Tobe T., Deelen M., Klaassen I., Grave W., Emmen M., Janssen W., Bossen W., Elzinga B., Van Der Velden A., Hemmelder M., Slagman M., Waanders F., Viergever P., Boerema I., Potter Van Loon B., Muthert B., Geers T., Schollaert N., Van Weverwijk I., Veen P., Woittiez A., Krikken J., Kwakernaak A., Visser F., Navis G., Hoekstra F., Hawkins S., McGregor D., Usher J., MacGinley R., Schollum J., Ellis G., Voss D., Rosman J., Upjohn M., Panlilio N., Madhan K., Naicker V., Anderson E., Bushell M., Lumb N., Pepperell B., Sizeland P., Hayett S., Sullivan N., Tuffery C., Macdonald A., Ostapowicz T., Wessel-Aas T., Wessel-Aas H., Bjorbaek E., Bjorbaek R., Simso I., Oien C., Bergrem H., Espedal S., Kronborg J., Solbakken K., Rocke J., Aakervik O., Haugen V., Eide T., Berglund J., Loland W., Schei T., Stromsaether C., Willadsen H., Lyngdal P., Vad A., Waldum B., Froslid G., Roaldsnes C., Rustad D., Soderblom P., Eriksen B., Hanssen E., Julsrud J., Mathisen U., Pedersen M., Rumsfeld M., Toft I., Berget K., Landsverk K., Tveiten G., Wamstad H., Klinger M., Krajewska M., Golebiowski T., Kusztal M., Spiechowicz-Zaton U., Rutkowski B., Renke M., Tylicki L., Czekalski S., Koziol L., Wanic-Kossowska M., Wasik-Olejnik A., Nowicki M., Dryja P., Kurnatowska I., Zawiasa A., Ciszek M., Gomolka M., Mysliwiec M., Brzosko S., Mazerska M., Hruby Z., Koscielniak K., Stanek-Piotrowska M., Mesjasz J., Rudka R., Baranski M., Jupowiecki J., Klein D., Switalski M., Kuriga M., Ostrowski M., Lidman A., Linde T., Waltersson K., Weiss L., Andersson G., Lindell C., Welander G., Jacobson S., Edensjo P., Wallin J., Linder M., Karsberg M., Hellgren K., Lonn I., Frisenette-Fich C., Johansson A., Lundstrom A., Mauritz N., Stahl-Nilsson A., Tobafard N., Hellberg O., Ejemar E., Von Schmalensee N., Gunne T., Eriksson A., Ostberg S., Svensson C., Mulec H., Jacobsson A., Karlsson M., Onnermalm L., Osagie S., Ekengren U., Larsson M., Lindberger K., Olofsson A., Samuelsson O., Beagan L., Dezfoolian H., Just M., Ortegren L., Saeed A., Strand U., Ramsauer B., Hultstrom D., Nordlinder K., Sundberg I., Oqvist B., Green C., Fernstrom A., Cassel A., Goransson I., Gylling M., Jorgensen A., Sterner G., Christensson A., Hjelmstedt P., Nystrom A., Sundin P., Samuelsson I., Tidman M., Johansson M., Lofgren Andersson M., Ohman M., Andersson P., Hallberg Karlsson A., Ringstad L., Chittinandana A., Chailimpamontree W., Gojaseni P., Singprasert R., Tungsanga K., Amphun W., Intim P., Kanjanabuch T., Poowarattanakul D., Treratha C., Wongvan P., Jittikanont S., Suriya T., Indrasthitya P., Sumethkul V., Ingsathit A., Jansomwong J., Lertchalorarn K., Phachiyanukul V., Phiromkit T., Saengsri S., Vareesangthip K., Chawanasuntorapoj R., Kiattisunthorn K., Larpkitkachorn R., Webster J., Henderson J., Jayne D., Hollis J., Townsend K., Harron C., Bleakley N., Hanley N., Morgan S., Brittney L., Brown H., Maxwell P., Murtagh H., Thomas M., Burke E., Carmody M., Cox G., Dasgin J., Ali G., Whitehouse L., Williams V., Brown E., Dlelana G., Esson A., Fagerbrink S., Marshall F., Mazibuko B., Nelson C., Russell E., Williams R., Altmann P., McNichols-Thomas C., Parsons K., MacGregor M., McGowan J., Mead P., Gilbanks K., Sanderson M., Fluck R., Chandler G., Hulme L., Smith J., Tse Y., West C., Taylor J., Breakspear S., Burgess B., Isles C., Bell J., Duignan J., Gorman J., Swainson C., Beveridge C., Cairns A., Miller D., Paterson F., Smith L., Kumwenda M., Glover R., Geddes C., Gemmell C., Grieve I., Matthews E., McLaren B., Meyer B., Spiers A., Banks R., Apperley P., Patterson T., Paynter H., Scoble J., Thom D., Watkins J., Kalra P., Gowland S., Haydock L., Smart I., Bhandari S., Gillett P., James K., Lewis R., Melville H., Tamimi A., Williams P., Heath T., Small S., Paterson A., Gibson N., Laven C., Wilson T., Cairns H., Casley-Ready K., Warwick G., Fentum B., James J., Kumar T., Marshall R., Ratcliffe F., Shenton A., Warwicker P., Bowser M., Mumford C., Mitra S., Woolfson R., Yang R., Williams A., Richards K., Turner A., Odum J., Rylance P., Smallwood A., Ward J., Henderson I., McMahon M., Ross C., Burrows M., Morais J., Rajan S., Tindall H., Barrett C., Kelly F., El-Nahas M., Bartholomew J., Edwards L., Okhuoya F., Bebb C., Cassidy M., Brand S., Quashie-Howard M., Taggart C., Capps N., Tonks L., Mason J., Powell S., Watkins L., Ball S., Dutton M., Fifer L., McGlynn F., Wood M., Jenkins D., Allan N., Fahal I., Elhag-Ali H., King J., Peel R., Potts L., Logie I., McGhie F., Naik R., Parry R., Andain K., Durkin S., D'Souza R., Harrison D., Cooke J., Kinyanjui R., Harper J., Algate K., McCarthy M., Van Eker D., Thuraisingham R., Chinodya M., Deelchand V., Garcia R., Ngango R., Rolfe C., Williams K., Solomon L., Heap T., MacDowall P., Saunderson Smith L., MacDiarmaid-Gordon A., Harman W., Smithson H., Robertson D., Gammon B., O'Grady D., Verow C., Rogerson M., Berry L., Gough C., Hayward E., Jones C., Payne T., Rowe L., Sibley C., Szymanski J., Almond M., Bourton L., Bromwich C., Dawson S., Mason S., Oliveira D., Ramkhelawon R., Tuazon J., Andrews P., Archer K., Moore A., Thomas G., Velazquez C., Mumtaz R., Roberts R., Farquhar F., Ott J., Fenwick S., Callaway A., Garrett P., Dees L., McDonagh U., Garner S., Zehnder D., Aldridge N., Dyer C., Gomez M., Hewins S., McCarthy K., Rush J., Spencer S., Harvey M., Mills H., Drew P., Henry M., Wilberforce S., Worth D., Adair Z., Hartley J., Jibani M., Jones D., Swan S., Shamp T., Alcorn H., Bookey J., Cannon C., Jarvis K., Muesing C., Murphy M., Muster H., Planting M., Strand C., Middleton J., Gitter K., Mace N., Schumm D., Pogue V., Alimohammadi B., Arora P., Herbert L., Cheng J., Dowie D., Mohan S., Peters G., Tuttle K., Albritton S., Benedetti R., Joshi S., Lund B., Shuler L., Trevino M., Mai K., Osborn T., Parekh R., Eustace J., Novak G., Patterson S., Lindsey C., Hill T., Liston M., Wiegmann T., Nagaria A., Hurd C., Hurst A., Omoscharka E., Parks S., and Price V.
- Abstract
Background: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Method(s): Patients with advanced CKD (blood creatinine >=1.7 mg/dL [>= 150 mumol/L] in men or >=1.5 mg/dL [ >= 130 mumol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. Results A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. Conclusions SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.Copyright © 2010, Mosby, Inc. All rights reserved.
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- 2010
8. Cost effectiveness of herpes simplex virus type 2 serologic testing and antiviral therapy in pregnancy.
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Baker D, Brown Z, Hollier LM, Wendel GD Jr., Hulme L, Griffiths DA, and Mauskopf J
- Abstract
OBJECTIVE: The purpose of this study was to determine whether serologic testing for herpes simplex virus type 2 (HSV-2) in pregnant women and their partners is cost-effective. STUDY DESIGN: A decision analysis model was developed to investigate the cost-effectiveness of providing type-specific serologic testing at week 15 of pregnancy for all women unaware of their HSV-2 status, and offering antiviral suppressive therapy from week 36 until delivery to all seropositive women. This scenario was compared with current care, in which only a minority of women diagnosed with genital herpes (GH) receives antiviral suppressive therapy (AST). In a third scenario, testing is offered to partners of pregnant women who test seronegative, and antiviral suppressive therapy is offered to the partners who test seropositive. RESULTS: Compared with current care, offering testing and antiviral suppressive therapy to 100,000 pregnant women resulted in an incremental cost of $3.1 million, 15.7 fewer cases of neonatal herpes, 186 fewer cesarean deliveries, and an incremental cost per quality-adjusted life- year gained (QALY) of $18,680. Offering testing and suppressive therapy to both the pregnant women and their partners resulted in an increased cost of $8.6 million, 16.8 fewer cases of neonatal herpes, 192 fewer cesarean deliveries, and an incremental cost per QALY of $48,946 compared with no testing. CONCLUSION: Compared with commonly accepted benchmarks for cost-effectiveness (<$50,000/QALY), type-specific HSV-2 serologic testing of pregnant women may be a cost-effective Copyright © 2004 by Elsevier Science (USA). [ABSTRACT FROM AUTHOR]
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- 2004
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9. Solvent effects in the spectra of Benzene, Toluene, and Chlorobenzene at 2600 and 2000 A.
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Bayliss, NS and Hulme, L
- Abstract
The ultraviolet spectra of benzene, toluene, and chlorobenzene at 2600 and 2000 Ǻ have been measured in carbon tetrachloride, chloroform, cyclohexane, 1%-hexane, ethanol, and water. Compared with the gases the solution spectra are all displaced to the red by amounts that agree qualitatively with the predicted effect of the solvent refractive index and the transition intensity according to the theory of Bayliss (1950). Quantitative agreement with this theory can be obtained only by assuming the effective cavity occupied by the solute molecule to be considerably smaller than the actual molecular size. The significance of this effect is discussed. The intensities of the solution spectra vary with the solvent refractive index, but in a way that is incompatible with the classical theory of Chako (1934). A marked increase in the intensity (particularly in toluene) is found where the solute absorption is close to an absorption band of the solvent, that is, for the 2600 Ǻ transitions in carbon tetrachloride and to a less extent in chloroform. In the 2600 Ǻ transition of benzene, a band appears in water, chloroform, and carbon tetrachloride that is very close to the position of the (0,0) band that is forbidden in the gas spectrum. The nature of this band is discussed.
- Published
- 1953
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10. The 2016 Kumamoto Earthquakes: Cascading Geological Hazards and Compounding Risks
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Goda, K, Campbell, G, Hulme, L, Ismael, B, Ke, L, Marsh, R, Sammonds, P, So, E, Okumura, Y, Kishi, N, Koyama, M, Yotsui, S, Kiyono, J, Wu, S, and Wilkinson, S
- Subjects
2016 Kumamoto earthquake ,ground deformation ,13. Climate action ,earthquake damage survey ,surface rupture ,ground motion ,building damage ,infrastructure damage - Abstract
A sequence of two strike-slip earthquakes occurred on April 14 and 16, 2016 in the intraplate region of Kyushu Island, Japan, apart from subduction zones, and caused significant damage and disruption to the Kumamoto region. The analyses of regional seismic catalog and available strong motion recordings reveal striking characteristics of the events, such as migrating seismicity, earthquake surface rupture, and major foreshock-mainshock earthquake sequences. To gain valuable lessons from the events, a UK Earthquake Engineering Field Investigation Team (EEFIT) was dispatched to Kumamoto, and earthquake damage surveys were conducted to relate observed earthquake characteristics to building and infrastructure damage caused by the earthquakes. The lessons learnt from the reconnaissance mission have important implications on current seismic design practice regarding the required seismic resistance of structures under multiple shocks and the seismic design of infrastructure subject to large ground deformation. The observations also highlight the consequences of cascading geological hazards on community resilience. To share the gathered damage data widely, geo-tagged photos are organized using Google Earth and the kmz file is made publicly available.
11. The distribution and habitat associations of non-native plant species in urban riparian habitats
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Maskell, Bullock, Smart, Thompson, Hulme, L. C., J. M., S. M., K., P. E., Maskell and Chiarucci, A.
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- 2006
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12. Creating a rewarding research experience in the early-career stages: Challenges and insights from the rEACH Summer School participants.
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de Lange S, Kearns A, Führer L, Dobbe JHM, Mielke K, Hulme L, Lim A, Oueslati R, Acampora M, De Mol Z, and Khaleghzadegan S
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- Humans, Schools, Career Choice
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- 2024
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13. Inhibition of serum- and glucocorticoid-induced kinase 1 ameliorates hydrocephalus in preclinical models.
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Hochstetler A, Smith H, Reed M, Hulme L, Territo P, Bedwell A, Persohn S, Perrotti N, D'Antona L, Musumeci F, Schenone S, and Blazer-Yost BL
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- Humans, Animals, Rats, Glucocorticoids, Phosphorylation, Biological Transport, Hydrocephalus drug therapy, Brain Injuries, Traumatic
- Abstract
Background: Hydrocephalus is a pathological accumulation of cerebrospinal fluid (CSF), leading to ventriculomegaly. Hydrocephalus may be primary or secondary to traumatic brain injury, infection, or intracranial hemorrhage. Regardless of cause, current treatment involves surgery to drain the excess CSF. Importantly, there are no long-term, effective pharmaceutical treatments and this represents a clinically unmet need. Many forms of hydrocephalus involve dysregulation in water and electrolyte homeostasis, making this an attractive, druggable target., Methods: In vitro, a combination of electrophysiological and fluid flux assays was used to elucidate secretory transepithelial electrolyte and fluid flux in a human cell culture model of the choroid plexus epithelium and to determine the involvement of serum-, glucocorticoid-induced kinase 1 (SGK1). In vivo, MRI studies were performed in a genetic rat model of hydrocephalus to determine effects of inhibition of SGK1 with a novel inhibitor, SI113., Results: In the cultured cell line, SI113 reduced secretory transepithelial electrolyte and fluid flux. In vivo, SI113 blocks the development of hydrocephalus with no effect on ventricular size of wild-type animals and no overt toxic effects. Mechanistically, the development of hydrocephalus in the rat model involves an increase in activated, phosphorylated SGK1 with no change in the total amount of SGK1. SI113 inhibits phosphorylation with no changes in total SGK1 levels in the choroid plexus epithelium., Conclusion: These data provide a strong preclinical basis for the use of SGK1 inhibitors in the treatment of hydrocephalus., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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14. Patients' Views on Medical Events in Lung Cancer Screening as Teachable Moments for Smoking Behaviour Change: A Systematic Review and Metasynthesis.
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Vikram A, Muller C, and Hulme L
- Abstract
Although medical events in lung cancer screening (LCS) such as receiving scan results or interactions with clinicians are recognised as teachable moments (TMs), the views of patients about why this is the case for smoking behaviour change remain uncertain. This systematic review and metasynthesis study is aimed at identifying the reasons why patients believed that medical events during LCS act as TMs for smoking behaviour change. A search strategy was developed for use with MEDLINE, PsycINFO, EMBASE, CINAHL-P, Web of Science databases, and Google Scholar. This helped identify qualitative and mixed-method research which mentioned patients' views of how these TMs result in smoking behaviour change. After screening, final articles were critically appraised; general characteristics and data relevant to the aims were extracted to conduct a line-of-argument metasynthesis. After screening 695 papers, 11 were included. Undergoing LCS scans was seen to act on their intrinsic motivation to reduce smoking as it served as a "wake-up call" and increased awareness of the health consequences of smoking. Receiving positive or negative LCS results resulted in cessation as it was a "health scare" and challenged smoking habits. Interactions with clinicians addressed misconceptions and signposted them to specialist cessation services. Attendees believed that the following encouraged them to change their smoking behaviour: having an intrinsic motivation to quit, their beliefs on smoking and health reframed, their negative emotions appraised, and using LCS to access specialist support. In line with the TM heuristic, these experiences provided the necessary skills, confidence, and motivation to quit. Future research should explore whether the views of the clinicians match those of the attendees to address misconceptions and further develop clinical guidelines., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Anvita Vikram et al.)
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- 2023
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15. Characterization of TRPV4-mediated signaling pathways in an optimized human choroid plexus epithelial cell line.
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Hulme L, Hochstetler A, Schwerk C, Schroten H, Ishikawa H, Tung CY, Perrin B, and Blazer-Yost B
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- Humans, Cell Line, Blood-Brain Barrier metabolism, Membrane Transport Proteins metabolism, Signal Transduction, Epithelial Cells metabolism, TRPV Cation Channels genetics, TRPV Cation Channels metabolism, Choroid Plexus metabolism, Phosphatidylinositol 3-Kinases metabolism
- Abstract
The objectives of these studies were twofold: 1 ) to characterize the human choroid plexus papilloma (HIBCPP) cell line as a model of the blood-cerebrospinal fluid barrier (BCSFB) via morphology, tightness, and polarization of transporters in choroid plexus epithelia (CPe), and 2 ) to utilize Ussing-style electrophysiology to elucidate signaling pathways associated with the activation of the transient receptor potential vanilloid 4 (TRPV4) channel involved in cerebrospinal fluid (CSF) secretion. RT-PCR was implemented to determine gene expression of cell fate markers, junctional complex proteins, and transporters of interest. Scanning electron microscopy and confocal three-dimensional renderings of cultures grown on permeable supports were utilized to delineate the morphology of the brush border, junctional complexes, and polarization of key transporters. Electrophysiology was used to understand and explore TRPV4-mediated signaling in the HIBCPP cell line, considering both short-circuit current ( I
sc ) and conductance responses. HIBCPP cells grown under optimized culture conditions exhibited minimal multilayering, developed an intermediate resistance monolayer, retained differentiation properties, and expressed, and correctly localized, junctional proteins and native transporters. We found that activation of TRPV4 resulted in a robust, multiphasic change in electrogenic ion flux and increase in conductance accompanied by substantial fluid secretion. This response appears to be modulated by a number of different effectors, implicating phospholipase C (PLC), protein kinase C (PKC), and phosphoinositide 3-kinase (PI3K) in TRPV4-mediated ion flux. The HIBCPP cell line is a representative model of the human BCSFB, which can be utilized for studies of transporter function, intracellular signaling, and regulation of CSF production.- Published
- 2022
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16. Porcine choroid plexus-Riems cell line demonstrates altered polarization of transport proteins compared with the native epithelium.
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Hochstetler A, Hulme L, Delpire E, Schwerk C, Schroten H, Preston D, Simpson S, and Blazer-Yost BL
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- Animals, Blood-Brain Barrier metabolism, Cell Line, Cerebrospinal Fluid metabolism, Epithelium metabolism, Swine, Carrier Proteins metabolism, Choroid Plexus metabolism
- Abstract
The choroid plexus epithelium (CPe) forms a barrier between the cerebral blood supply and the cerebrospinal fluid (CSF), establishing the blood-CSF barrier (BCSFB). CSF is actively secreted by the CPe via tightly controlled processes involving multiple channels, transporters, and pumps. The importance of controlling CSF production and composition has been accentuated recently with an appreciation of CSF dysfunction in many pathologies. For mechanistic studies of CSF production, isolated CPe cell lines are valuable for the testing of hypotheses and potential drug targets. Although several continuous CPe cell lines have been described, none appear to have all the characteristics of the native epithelium and each must be used judiciously. The porcine choroid plexus-Riems (PCP-R) cell line forms a high-resistance monolayer characteristic of a barrier epithelium. Conservation of this phenotype is unusual among CPe cell lines, making this model useful for studies of the effects of infection, injury, and drugs on permeability. We have recently discovered that, although this line expresses many of the transporters expressed in the native tissue, some are mispolarized. As a result, inferences regarding fluid/electrolyte flux and the resultant CSF production should be pursued with caution. Furthermore, extended culture periods and changes in media composition result in significant morphological and functional variability. These studies provide a more detailed characterization of the PCP-R cell line concerning transporter expression, polarization, and functionality, as well as plasticity in culture, with the goal to provide the scientific community with information necessary to optimize future experiments with this model.
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- 2022
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17. Identification of undiagnosed atrial fibrillation patients using a machine learning risk prediction algorithm and diagnostic testing (PULsE-AI): Study protocol for a randomised controlled trial.
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Hill NR, Arden C, Beresford-Hulme L, Camm AJ, Clifton D, Davies DW, Farooqui U, Gordon J, Groves L, Hurst M, Lawton S, Lister S, Mallen C, Martin AC, McEwan P, Pollock KG, Rogers J, Sandler B, Sugrue DM, and Cohen AT
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- Algorithms, Electrocardiography, Heart Rate, Humans, Machine Learning, Mass Screening, Randomized Controlled Trials as Topic, Atrial Fibrillation diagnosis, Atrial Fibrillation epidemiology
- Abstract
Atrial fibrillation (AF) is associated with an increased risk of stroke, enhanced stroke severity, and other comorbidities. However, AF is often asymptomatic, and frequently remains undiagnosed until complications occur. Current screening approaches for AF lack either cost-effectiveness or diagnostic sensitivity; thus, there is interest in tools that could be used for population screening. An AF risk prediction algorithm, developed using machine learning from a UK dataset of 2,994,837 patients, was found to be more effective than existing models at identifying patients at risk of AF. Therefore, the aim of the trial is to assess the effectiveness of this risk prediction algorithm combined with diagnostic testing for the identification of AF in a real-world primary care setting. Eligible participants (aged ≥30 years and without an existing AF diagnosis) registered at participating UK general practices will be randomised into intervention and control arms. Intervention arm participants identified at highest risk of developing AF (algorithm risk score ≥ 7.4%) will be invited for a 12‑lead electrocardiogram (ECG) followed by two-weeks of home-based ECG monitoring with a KardiaMobile device. Control arm participants will be used for comparison and will be managed routinely. The primary outcome is the number of AF diagnoses in the intervention arm compared with the control arm during the research window. If the trial is successful, there is potential for the risk prediction algorithm to be implemented throughout primary care for narrowing the population considered at highest risk for AF who could benefit from more intensive screening for AF. Trial Registration: NCT04045639., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2020
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18. Relationship between hypoglycaemia, body mass index and quality of life among patients with type 1 diabetes: Observations from the DEPICT clinical trial programme.
- Author
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Gordon J, Beresford-Hulme L, Bennett H, Tank A, Edmonds C, and McEwan P
- Subjects
- Body Mass Index, Humans, Hypoglycemic Agents therapeutic use, Quality of Life, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 epidemiology, Hypoglycemia chemically induced, Hypoglycemia epidemiology, Hypoglycemia prevention & control
- Abstract
Aims: To demonstrate the relationships between hypoglycaemia, body mass index (BMI) and quality of life, and to examine the impact of dapagliflozin on patient-reported treatment satisfaction in patients with type 1 diabetes mellitus (T1DM), using data from the DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) clinical trial programme., Methods: A two-stage modelling approach, using a linear regression framework, was adopted to evaluate the relationship between hypoglycaemia, BMI and quality of life. Hypoglycaemia fear score (HFS) was modelled as a function of hypoglycaemic events (non-severe documented symptomatic and severe) and, subsequently, quality of life (as measured by the EQ-5D questionnaire) was modelled as a function of HFS and BMI. A linked evidence approach correlated the relationship between treatment, hypoglycaemic events and glycated haemoglobin (HbA1c), to the relationships captured within the regression models. The proportion of patients achieving increased patient-reported treatment satisfaction, as measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) total score, was compared between study arms., Results: Incident severe hypoglycaemia was associated with significantly higher HFS (coefficient estimate [CE] 14.62, P=0.004). The frequency of symptomatic hypoglycaemic events was associated with a significantly higher HFS (log transposed, CE 1.32, P=0.026). Higher HFS and higher BMI were both independently associated with a significantly lower EQ-5D score (HFS: CE -0.0024, P<0.001; BMI: CE -0.0026, P=0.016). Significantly higher proportions of dapagliflozin-treated patients achieved ≥3-point increases in DTSQ total score compared to patients in the placebo group., Conclusion: The results of this study demonstrated that increases in hypoglycaemia and BMI were associated with reduced quality of life in people with T1DM. Dapagliflozin-treated patients achieved a reduction in HbA1c whilst avoiding an increase in hypoglycaemic events. The results also showed that treatment with dapagliflozin was associated with an improvement in treatment satisfaction., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
19. Adverse Changes in HbA1c, Body Weight and Insulin Use in People with Type 1 Diabetes Mellitus Following Dapagliflozin Discontinuation in the DEPICT Clinical Trial Programme.
- Author
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Gordon J, Danne T, Beresford-Hulme L, Bennet H, Tank A, Edmonds C, Thorén F, Scheerer MF, and McEwan P
- Abstract
Introduction: Dapagliflozin is an orally active inhibitor of sodium-glucose co-transporter 2 (SGLT2) that is indicated for use in adults with type 1 diabetes (T1DM) (with a body mass index (BMI) of at least 27 kg/m
2 in Europe, no such BMI limit in Japan), when insulin alone does not provide adequate glycaemic control. The aim of this study was to evaluate changes in glycated haemoglobin (HbA1c), body weight and insulin dose following discontinuation of dapagliflozin for the management of T1DM in the DEPICT clinical trial programme., Methods: The interrelationship between treatment discontinuation, insulin requirement and outcomes post-discontinuation was evaluated using descriptive summary statistics and linear regression modelling. Data were analysed from individuals with T1DM discontinuing dapagliflozin in DEPICT-1 or DEPICT-2 (unplanned or end of study). HbA1c and body weight were measured over the 56-week study period (consisting of a 52-week treatment period and a 4-week follow-up period) at 4-8 weekly intervals. Following discontinuation of dapagliflozin, 1-year change in HbA1c (%) and weight (kg) following discontinuation of dapagliflozin was estimated; total daily insulin doses were descriptively summarised., Results: Of the 1059 individuals that received dapagliflozin during the DEPICT trials 91 met the eligibility criteria and were included in the analyses of HbA1c and body weight. The mean duration of follow-up was 209 days in both analyses. Following dapagliflozin discontinuation, estimated annualised changes in HbA1c and body weight were + 0.99% (95% CI 0.39, 1.59) and + 3.75 kg (1.65, 5.86), respectively. An increase in insulin dose was observed around the time of discontinuation; insulin dose in the 2-week post-discontinuation was + 3.6 IU and + 4.4 IU higher with dapagliflozin 5 mg and 10 mg than 2 weeks pre-discontinuation, respectively., Conclusion: Discontinuation of dapagliflozin is predicted to lead to clinically meaningful increases in HbA1c and body weight, in addition to higher insulin doses. These findings are important in the management of people with T1DM among whom insulin is the only existing pharmacological treatment option.- Published
- 2020
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20. Homologous recombination repair intermediates promote efficient de novo telomere addition at DNA double-strand breaks.
- Author
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Davé A, Pai CC, Durley SC, Hulme L, Sarkar S, Wee BY, Prudden J, Tinline-Purvis H, Cullen JK, Walker C, Watson A, Carr AM, Murray JM, and Humphrey TC
- Subjects
- Chromosomes, Fungal genetics, DNA Breaks, Double-Stranded, Exodeoxyribonucleases genetics, Gene Expression Regulation, Fungal genetics, Genome, Fungal genetics, Genomic Instability genetics, Loss of Heterozygosity genetics, Rad51 Recombinase genetics, Schizosaccharomyces genetics, DNA Helicases genetics, DNA-Binding Proteins genetics, Recombinational DNA Repair genetics, Schizosaccharomyces pombe Proteins genetics, Telomere genetics
- Abstract
The healing of broken chromosomes by de novo telomere addition, while a normal developmental process in some organisms, has the potential to cause extensive loss of heterozygosity, genetic disease, or cell death. However, it is unclear how de novo telomere addition (dnTA) is regulated at DNA double-strand breaks (DSBs). Here, using a non-essential minichromosome in fission yeast, we identify roles for the HR factors Rqh1 helicase, in concert with Rad55, in suppressing dnTA at or near a DSB. We find the frequency of dnTA in rqh1Δ rad55Δ cells is reduced following loss of Exo1, Swi5 or Rad51. Strikingly, in the absence of the distal homologous chromosome arm dnTA is further increased, with nearly half of the breaks being healed in rqh1Δ rad55Δ or rqh1Δ exo1Δ cells. These findings provide new insights into the genetic context of highly efficient dnTA within HR intermediates, and how such events are normally suppressed to maintain genome stability., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2020
- Full Text
- View/download PDF
21. The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe .
- Author
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Andreadis C, Hulme L, Wensley K, and Liu JL
- Subjects
- Carbon-Nitrogen Ligases chemistry, Cell Compartmentation genetics, Cytoplasm genetics, Gene Knockout Techniques, Mechanistic Target of Rapamycin Complex 2 genetics, Phosphorylation genetics, Protein Serine-Threonine Kinases chemistry, Protein Serine-Threonine Kinases genetics, Receptors, Corticotropin-Releasing Hormone chemistry, Schizosaccharomyces pombe Proteins chemistry, Schizosaccharomyces pombe Proteins genetics, Signal Transduction genetics, Transcription Factors chemistry, Transcription Factors genetics, Carbon-Nitrogen Ligases genetics, Mechanistic Target of Rapamycin Complex 1 genetics, Receptors, Corticotropin-Releasing Hormone genetics, Schizosaccharomyces genetics
- Abstract
CTP synthase (CTPS) has been demonstrated to form evolutionarily-conserved filamentous structures termed cytoophidia whose exact cellular functions remain unclear, but they may play a role in intracellular compartmentalization. We have previously shown that the mammalian target of rapamycin complex 1 (mTORC1)-S6K1 pathway mediates cytoophidium assembly in mammalian cells. Here, using the fission yeast Schizosaccharomyces pombe as a model of a unicellular eukaryote, we demonstrate that the target of rapamycin (TOR)-signaling pathway regulates cytoophidium formation (from the S. pombe CTPS ortholog Cts1) also in S. pombe Conducting a systematic analysis of all viable single TOR subunit-knockout mutants and of several major downstream effector proteins, we found that Cts1 cytoophidia are significantly shortened and often dissociate when TOR is defective. We also found that the activities of the downstream effector kinases of the TORC1 pathway, Sck1, Sck2, and Psk1 S6, as well as of the S6K/AGC kinase Gad8, the major downstream effector kinase of the TORC2 pathway, are necessary for proper cytoophidium filament formation. Interestingly, we observed that the Crf1 transcriptional corepressor for ribosomal genes is a strong effector of Cts1 filamentation. Our findings connect TOR signaling, a major pathway required for cell growth, with the compartmentalization of the essential nucleotide synthesis enzyme CTPS, and we uncover differences in the regulation of its filamentation among higher multicellular and unicellular eukaryotic systems., (© 2019 Andreadis et al.)
- Published
- 2019
- Full Text
- View/download PDF
22. S. cerevisiae Srs2 helicase ensures normal recombination intermediate metabolism during meiosis and prevents accumulation of Rad51 aggregates.
- Author
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Hunt LJ, Ahmed EA, Kaur H, Ahuja JS, Hulme L, Chou TC, Lichten M, and Goldman ASH
- Subjects
- DNA Helicases metabolism, MAP Kinase Kinase 1 metabolism, Microbial Viability genetics, Mutation, Protein Aggregates, Protein Binding, Saccharomyces cerevisiae Proteins metabolism, Spores, Fungal, DNA Helicases genetics, Meiosis, Rad51 Recombinase metabolism, Recombination, Genetic, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics
- Abstract
We investigated the meiotic role of Srs2, a multi-functional DNA helicase/translocase that destabilises Rad51-DNA filaments and is thought to regulate strand invasion and prevent hyper-recombination during the mitotic cell cycle. We find that Srs2 activity is required for normal meiotic progression and spore viability. A significant fraction of srs2 mutant cells progress through both meiotic divisions without separating the bulk of their chromatin, although in such cells sister centromeres often separate. Undivided nuclei contain aggregates of Rad51 colocalised with the ssDNA-binding protein RPA, suggesting the presence of persistent single-strand DNA. Rad51 aggregate formation requires Spo11-induced DSBs, Rad51 strand-invasion activity and progression past the pachytene stage of meiosis, but not the DSB end-resection or the bias towards interhomologue strand invasion characteristic of normal meiosis. srs2 mutants also display altered meiotic recombination intermediate metabolism, revealed by defects in the formation of stable joint molecules. We suggest that Srs2, by limiting Rad51 accumulation on DNA, prevents the formation of aberrant recombination intermediates that otherwise would persist and interfere with normal chromosome segregation and nuclear division.
- Published
- 2019
- Full Text
- View/download PDF
23. Asymmetric inheritance of cytoophidia in Schizosaccharomyces pombe.
- Author
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Zhang J, Hulme L, and Liu JL
- Abstract
A general view is that Schizosaccharomyces pombe undergoes symmetric cell division with two daughter cells inheriting equal shares of the content from the mother cell. Here we show that CTP synthase, a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTP, can form filamentous cytoophidia in the cytoplasm and nucleus of S. pombe cells. Surprisingly, we observe that both cytoplasmic and nuclear cytoophidia are asymmetrically inherited during cell division. Our time-lapse studies suggest that cytoophidia are dynamic. Once the mother cell divides, the cytoplasmic and nuclear cytoophidia independently partition into one of the two daughter cells. Although the two daughter cells differ from one another morphologically, they possess similar chances of inheriting the cytoplasmic cytoophidium from the mother cell, suggesting that the partition of cytoophidium is a stochastic process. Our findings on asymmetric inheritance of cytoophidia in S. pombe offer an exciting opportunity to study the inheritance of metabolic enzymes in a well-studied model system., (© 2014. Published by The Company of Biologists Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
24. A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice.
- Author
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Pai CC, Deegan RS, Subramanian L, Gal C, Sarkar S, Blaikley EJ, Walker C, Hulme L, Bernhard E, Codlin S, Bähler J, Allshire R, Whitehall S, and Humphrey TC
- Subjects
- Acetylation, Methylation, Schizosaccharomyces metabolism, Acetyltransferases metabolism, Chromatin metabolism, DNA End-Joining Repair, DNA Repair, DNA, Fungal metabolism, Histone-Lysine N-Methyltransferase metabolism, Histones metabolism, Recombinational DNA Repair, Schizosaccharomyces genetics, Schizosaccharomyces pombe Proteins metabolism
- Abstract
DNA double-strand break (DSB) repair is a highly regulated process performed predominantly by non-homologous end joining (NHEJ) or homologous recombination (HR) pathways. How these pathways are coordinated in the context of chromatin is unclear. Here we uncover a role for histone H3K36 modification in regulating DSB repair pathway choice in fission yeast. We find Set2-dependent H3K36 methylation reduces chromatin accessibility, reduces resection and promotes NHEJ, while antagonistic Gcn5-dependent H3K36 acetylation increases chromatin accessibility, increases resection and promotes HR. Accordingly, loss of Set2 increases H3K36Ac, chromatin accessibility and resection, while Gcn5 loss results in the opposite phenotypes following DSB induction. Further, H3K36 modification is cell cycle regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs, while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. These findings support an H3K36 chromatin switch in regulating DSB repair pathway choice.
- Published
- 2014
- Full Text
- View/download PDF
25. The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.
- Author
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Blaikley EJ, Tinline-Purvis H, Kasparek TR, Marguerat S, Sarkar S, Hulme L, Hussey S, Wee BY, Deegan RS, Walker CA, Pai CC, Bähler J, Nakagawa T, and Humphrey TC
- Subjects
- Cell Cycle Checkpoints, Checkpoint Kinase 2 metabolism, Chromosomes, Fungal genetics, Comparative Genomic Hybridization, Exodeoxyribonucleases metabolism, Genome, Fungal, Loss of Heterozygosity, Nucleotides biosynthesis, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism, DNA Breaks, Double-Stranded, DNA Cleavage, Genomic Instability, Recombinational DNA Repair, Schizosaccharomyces genetics
- Abstract
DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3(ATR), Rad26ATRIP, Crb2(53BP1) or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low levels of chromosome loss, suggesting the 9-1-1 complex acts as a nuclease processivity factor to facilitate extensive resection. Further, our data suggest redundant roles for Rad3ATR and Exo1 in facilitating extensive resection. We propose that the DNA damage checkpoint pathway coordinates resection and nucleotide synthesis, thereby promoting efficient HR repair and genome stability., (© The Author(s) 2014. Published by Oxford University Press.)
- Published
- 2014
- Full Text
- View/download PDF
26. Automated peritoneal dialysis has significant effects on systemic hemodynamics.
- Author
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Selby NM, Fonseca S, Hulme L, Fluck RJ, Taal MW, and McIntyre CW
- Subjects
- Aged, Aged, 80 and over, Automation, Blood Pressure physiology, Female, Humans, Kidney Failure, Chronic etiology, Kidney Failure, Chronic therapy, Male, Middle Aged, Hemodynamics physiology, Peritoneal Dialysis methods, Peritoneal Dialysis, Continuous Ambulatory methods
- Abstract
Objectives: Maintenance of residual renal function (RRF) is an important determinant of outcome in peritoneal dialysis patients. It remains contentious as to whether automated peritoneal dialysis (APD) leads to an increased rate of decline of RRF compared with continuous ambulatory peritoneal dialysis (CAPD). We studied whether APD was associated with significant systemic hemodynamic changes that may play a role in the accelerated loss of RRF., Methods: As a follow-on from a previous study, 8 well-established CAPD patients underwent a 4-hour APD treatment consisting of 3 drain/fill cycles using 2 x 2.5 L 1.36% glucose and 1 x 3.86% glucose dialysate. Each dwell phase lasted 76 minutes. Blood pressure (BP) and a full range of hemodynamic variables, including pulse (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR), were measured noninvasively using continuous arterial pulse wave analysis., Results: BP fell during 2 of the 3 drain/fill periods when dialysate was drained from the peritoneal cavity, but then rose upon instillation of dialysate fluid. The fall in BP was associated with a fall in TPR, matched by an inadequate rise in SV and CO. Over the entire study period, TPR progressively rose to +53.4% above baseline (p = 0.032). Both SV and CO fell over the same period, to -21.1% (p = 0.060) and -22.4% from baseline (p = 0.037) respectively. This did not result in any significant difference between start and end BP., Conclusions: This study demonstrates that APD is associated with significant systemic hemodynamic effects. The increased number of drain/fill cycles compared to CAPD, or the progressive rise in TPR and reduction in CO (possibly due to a cooling effect), may potentially be factors that adversely affect RRF in APD patients.
- Published
- 2006
27. Cost-effectiveness of rosiglitazone combination therapy for the treatment of type 2 diabetes mellitus in the UK.
- Author
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Beale S, Bagust A, Shearer AT, Martin A, and Hulme L
- Subjects
- Combined Modality Therapy, Diabetes Complications, Diabetes Mellitus, Type 2 economics, Drug Therapy, Combination, Economics, Pharmaceutical, Female, Glycated Hemoglobin drug effects, Humans, Hypoglycemic Agents economics, Male, Obesity complications, Obesity economics, Quality-Adjusted Life Years, Rosiglitazone, Thiazolidinediones economics, United Kingdom, Cost-Benefit Analysis, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Metformin therapeutic use, Models, Economic, Thiazolidinediones therapeutic use
- Abstract
Introduction: Recent clinical trial results have demonstrated that, in patients with type 2 diabetes, second-line treatment of rosiglitazone in combination with metformin can lead to significant improvements in the control of fasting plasma glucose/ glycosylated haemoglobin A1c (HbA1c) after the failure of metformin monotherapy. Our objective was to assess the cost-effectiveness of the use of rosiglitazone in combination with metformin in overweight and obese patients with type 2 diabetes in the UK, failing to maintain glycaemic control with metformin monotherapy compared with conventional care using metformin in combination with sulfonylurea., Methods: The Diabetes Decision Analysis of Cost--type 2 (DiDACT) model, an established long-term economic model of type 2 diabetes, which projects the relationship between treatment and HbA1c over extended periods, was used to determine the health outcomes and economic impact for matched age and sex cohorts of 1000 patients with type 2 diabetes. The perspective was that of the UK National Health Service and all costs were in UK pounds sterling., Results: Treatment with rosiglitazone in combination with metformin provides better glycaemic control over the remaining lifetime of patients than metformin and sulfonylurea combination therapy. Patients treated with rosiglitazone combination therapy were predicted to have a longer life expectancy, gaining 123 and 140 additional life years per 1000 patients in the obese and overweight cohorts, respectively. Improvements in morbidity and a delay in the start of insulin therapy resulted in a projected improvement in quality of life. These effects combine with projected improved survival to yield 131 and 209 additional quality-adjusted life-years (QALYs) per 1000 patients in the obese and overweight cohorts, respectively. Discounted incremental cost-effectiveness ratios were estimated at pounds 16,700 per QALY gained for the obese cohort and pounds 11,600 per QALY gained for the overweight cohort., Conclusion: The model predicts that rosiglitazone in combination with metformin is a cost-effective treatment in the UK for both obese and overweight patients failing on metformin monotherapy, compared with conventional therapy using metformin in combination with sulfonylurea.
- Published
- 2006
- Full Text
- View/download PDF
28. Hypertonic glucose-based peritoneal dialysate is associated with higher blood pressure and adverse haemodynamics as compared with icodextrin.
- Author
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Selby NM, Fonseca S, Hulme L, Fluck RJ, Taal MW, and McIntyre CW
- Subjects
- Aged, Aged, 80 and over, Cross-Over Studies, Diabetes Mellitus, Type 2 classification, Female, Humans, Icodextrin, Male, Middle Aged, Glucans, Glucose, Hemodialysis Solutions, Hemodynamics physiology, Hypertension epidemiology, Kidney Failure, Chronic physiopathology, Kidney Failure, Chronic therapy, Peritoneal Dialysis, Continuous Ambulatory adverse effects
- Abstract
Background: Little is known about the haemodynamic effects of continuous ambulatory peritoneal dialysis (CAPD) despite its widespread use in the management of end-stage renal failure. We undertook a study to delineate the haemodynamic effects of CAPD using glucose-containing fluids (1.36 and 3.86% glucose) and icodextrin., Methods: Eight CAPD patients were recruited for a prospective crossover study. Patients attended for two investigatory days (in random order). CAPD was carried out using 1.36% followed by 3.86% glucose (buffered with lactate/bicarbonate, Physioneal) on one study day and 1.36% glucose followed by 7.5% icodextrin (Extraneal) on the other day. Dwell times were 150 min. Blood pressure (BP) and a full range of haemodynamic variables including pulse (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were measured non-invasively using continuous arterial pulse wave analysis., Results: BP was significantly higher during 3.86% glucose dwells as compared with 1.36% glucose or icodextrin dwells (P<0.0001). TPR during all three dwells was similar; the higher blood pressure was due to an increased HR, SV and, therefore, CO during 3.86% glucose dwells. The higher blood pressure during the 3.86% glucose dwells was present despite the highest ultrafiltration volume and sodium removal., Conclusion: This study demonstrates large magnitude haemodynamic changes in response to CAPD. In addition to the well-recognized adverse effects on blood glucose and long-term peritoneal membrane viability, CAPD fluids containing high glucose concentrations may also exert undesirable effects on systemic haemodynamics, with potential long-term consequences for patient outcomes.
- Published
- 2005
- Full Text
- View/download PDF
29. Reflections on a working life. Interview by Heather Witham.
- Author
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Hulme L
- Subjects
- History, 20th Century, Hospitals, Urban history, Humans, Victoria, Nursing Staff, Hospital history, Students, Nursing history
- Published
- 1999
30. The potential usefulness of a differentiating teratocarcinoma cell line in in vitro toxicity testing.
- Author
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Hulme LM, Atkinson KA, Clothier RH, and Balls M
- Abstract
A number of in vitro systems have been put forward as potential alternative methods for testing chemicals for teratogenic potential. The most promising of these systems, for example mammalian whole embryo culture and the micromass technique, are currently undergoing further interlaboratory validation. However, such tests involve the use of a considerable number of animals. It was therefore decided to investigate the possible use of a permanent cell line that possessed many of the properties of embryonic cells, that is a differentiating cell line, F9 (derived from a mouse teratocarcinoma), in the development of an in vitro teratogenicity test. In a preliminary study, six chemicals were tested for their modulating effects on differentiation in undifferentiated, differentiating and differentiated F9 cells. These effects were assessed morphologically and by measuring the production of laminin (a biochemial marker of F9 differentiation). The use of the F9 cell line in in vitro teratogenicity testing shows promise, but further work is necessary before its potential can be fully evaluated.
- Published
- 1990
- Full Text
- View/download PDF
31. Assessment of two alternative methods for predicting the in vivo toxicities of metallic compounds.
- Author
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Hulme LM, Reeves HL, Clothier RH, Smith M, and Balls M
- Subjects
- Animals, Cell Survival drug effects, Lethal Dose 50, Mice, Rats, Metals toxicity, Toxicology methods
- Abstract
The FRAME in vitro cytotoxicity assay and a physicochemical parameter for metal ions (i.e., "softness," sigma p) were assessed for their ability to predict the in vivo acute toxicities of 52 metallic compounds. The in vitro assay was found to be more useful, since it measures the toxicity of the whole compound, as does the in vivo method. The softness parameter applies to the metal ion only, so it cannot be used to predict the toxicity of compounds containing relatively nontoxic metal ions and toxic anions (e.g., potassium fluoride). The in vitro toxicity values (expressed as ID50 values, i.e., concentrations of test chemicals that reduced the final cellular protein content of test cultures by 50% in comparison with appropriate solvent control cultures) correlated better with mouse ip LD50 values than with rat oral LD50 values.
- Published
- 1987
32. Comparison of the in vitro cytotoxicities and acute in vivo toxicities of 59 chemicals.
- Author
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Clothier RH, Hulme LM, Smith M, and Balls M
- Subjects
- Administration, Oral, Animals, Injections, Intraperitoneal, Lethal Dose 50, Mice, Rats, Cell Survival drug effects, Toxicology methods
- Abstract
The in vitro cytotoxicities of 59 chemicals, expressed as ID50 values (i.e., concentrations of test chemicals that reduced the final cellular protein content of test cultures by 50% in comparison with appropriate solvent control cultures) and obtained using murine 3T3-L1 cells and the FRAME kenacid blue method, have been compared with rat oral and mouse intraperitoneal (ip) LD50 values. A better in vivo/in vitro correlation was obtained for the 59 chemicals with mouse ip LD50 values (r = .80) than with rat oral LD50 values (r = .76), but the best in vivo/in vitro correlation was found when the most toxic of the rat and mouse values were used in the comparison (r = .81).
- Published
- 1987
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