90 results on '"Strand C"'
Search Results
2. Understanding the current backlash against LGBTIQ+ rights through the lens of heteroactivism: A case study of the International Organization for the Family’s transnational norm diffusion on Twitter
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Strand Cecilia, Eriksson Åsa, and Svensson Jakob
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anti-gender ,digital media ,heteroactivism ,lgbtiq+ ,norm diffusion ,Communication. Mass media ,P87-96 - Abstract
A new generation of transnational anti-gender actors are framing themselves as human rights champions and protectors of the rights of the “natural family”. To better understand these actors’ norm diffusion, including their re-styling of anti-gender narratives in contemporary iterations of heteroactivism and its potential threat to LGBTIQ+ rights, in this article we analyse the social media tactics of a key transnational anti-gender actor: the International Organization for the Family (IOF). The analysis is focused on the organisation’s Twitter (now X) account and we draw on theories of network media logic, connective action, and connective emotions. Two periods of activism – the first a low-intensity period in 2021 and the second a high-intensity period in 2022 – were purposefully selected for the analysis. In this article, we identify differences between the two periods, noting that the period covering the flagship event, the World Congress of Families (WCF) in 2022, was markedly less LGBTIQ-hostile and adversarial than the first period. IOF thus appears to be inspired by heteroactivist frames during the WCF and abides by logic that should trigger user interaction and content spreading. The lack of interactions and engagement with IOF Twitter content in either period indicates the need for more research on which logics apply to anti-gender audiences. We discuss the findings and what they may imply in a context like Sweden, a country whose self-image as a global champion for women’s and LGBTIQ+ rights may make it ill-equipped to counter the onslaught of transnational actors’ norm entrepreneurial activities.
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- 2024
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3. Drugs and Remedies
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Strand, C. Vibeke and Clark, Sharon R.
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- 1983
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4. Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy
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Paviour, D. C., Lees, A. J., Josephs, K. A., Ozawa, T., Ganguly, M., Strand, C., Godbolt, A., Howard, R. S., Revesz, T., and Holton, J. L.
- Published
- 2004
5. Pathological, clinical and genetic heterogeneity in progressive supranuclear palsy
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Morris, H. R., Gibb, G., Katzenschlager, R., Wood, N. W., Hanger, D. P., Strand, C., Lashley, T., Daniel, S. E., Lees, A. J., Anderton, B. H., and Revesz, T.
- Published
- 2002
6. Multiphysics Analysis of CFRP Charpy Tests by varying Temperatures.
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Andleeb, Z., Strand, C., Malik, S., Hussain, G., Khawaja, H., Boiger, G., and Moatamedi, M.
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NOTCHED bar testing , *WOVEN composites , *MECHANICAL properties of condensed matter , *LOW temperatures , *YOUNG'S modulus - Abstract
Carbon Fiber Reinforced Polymer (CFRP) composites have emerged as a major class of structural materials that have a significant potential use as a substitute for metals in aerospace, marine, automotive, and architecture due to their higher-strength-to-weight-ratio. CFRP is well suited for various applications, but their mechanical properties such as 'low-velocity impact resistance' are not well studied. In this study, the low-velocity impact resistance of CFRP woven composite was investigated with the help of Charpy impact tests. The CFRP samples were tested at room temperature (22°C) and at low temperature (-20°C). The experimental results indicated about 10% drop in energy-absorbing capability of CFRP samples at low temperatures in comparison to room temperature. The experimental results obtained for the room temperature were validated through finite element simulations using ANSYS® Workbench Explicit Dynamics. The mesh sensitivity analysis was performed to improve the accuracy of the finite element model. The numerical results helped to narrow down on the CFRP material properties that changed with temperature drop. It was found at -20°C, orthotropic Elasticity (Young's moduli in three mutually perpendicular directions) increases for CFRP woven composite as compared to room temperature (22°C), however the CFRP become brittle and there is a significant drop in their toughness. The current outcomes are useful for applications using CFRP under impact loading at low temperatures. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
- View/download PDF
7. Minimal disease activity for rheumatoid arthritis: A preliminary definition
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Wells, G. A., Boers, M., Shea, B., Brooks, P. M., Simon, L. S., Strand, C. V., Aletaha, D., Anderson, J. J., Bombardier, C., Dougados, M., Emery, P., Felson, D. T., Fransen, J., Furst, D. E., Hazes, J. M. W., Johnson, K. R., Kirwan, J. R., Landewé, R. B. M., Lassere, M. N. D., Michaud, K., Suarez-Almazor, M., Silman, A. J., Smolen, J. S., Heijde, D. M. F. M., Riel, P. L. C. M., Wolfe, F., Peter Tugwell, Rheumatology, and Other departments
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Pathogenesis and modulation of inflammation [N4i 1] ,Chronic inflammation and autoimmunity [UMCN 4.2] ,musculoskeletal diseases ,Arthritis, Rheumatoid ,Clinical Trials as Topic ,Treatment Outcome ,ROC Curve ,Evaluation of complex medical interventions [NCEBP 2] ,Outcome Assessment, Health Care ,Humans ,skin and connective tissue diseases ,Auto-immunity, transplantation and immunotherapy [N4i 4] ,Severity of Illness Index - Abstract
Contains fulltext : 48816.pdf (Publisher’s version ) (Closed access) Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.
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- 2005
8. Photographs of MIT environments
- Author
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Brian J. Swift., Massachusetts Institute of Technology. Dept. of Architecture., Strand, C. Mark, Brian J. Swift., Massachusetts Institute of Technology. Dept. of Architecture., and Strand, C. Mark
- Abstract
Thesis (M.S.V.S.)--Massachusetts Institute of Technology, Dept. of Architecture, 1984., MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH., This thesis is based on an exhibition of 43 photographs shown in a visual thesis exhibition at the Creative Photography Gallery November 15-December 15, 1983. The photographs document MIT environments with special categories pertaining to equipment and artifacts, working environments and portraits. The project is essentially a creative rather than a research project. It was undertaken in four semesters beginning in the fall of 1982. The thesis is a catalog of the exhibition with project background and technical notes . Slides of the photographs may be seen in the Rotch Visual Collections Library, and prints may be seen at the MIT Museum. Five of the exhibition prints (1), (21), (22), (39) and (42) were purchased for the Hayden Gallery permanent collection., by C. Mark Strand., M.S.V.S.
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- 2013
9. 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.
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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., 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., 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 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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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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
10. Measures of response in clinical trials of systemic sclerosis: the combined response index for systemic sclerosis (CRISS) and Outcome Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS)
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Khanna, D, Distler, O, Avouac, J, Behrens, F, Clements, P J, Denton, C, Foeldvari, I, Giannini, E, Huscher, D, Kowal-Bielecka, O, Lovell, D, Matucci-Cerinic, M, Mayes, M, Merkel, P A, Nash, P, Opitz, C F, Pittrow, D, Rubin, L, Seibold, J R, Steen, V, Strand, C V, Tugwell, P S, Varga, J, Zink, A, Furst, D E, Khanna, D, Distler, O, Avouac, J, Behrens, F, Clements, P J, Denton, C, Foeldvari, I, Giannini, E, Huscher, D, Kowal-Bielecka, O, Lovell, D, Matucci-Cerinic, M, Mayes, M, Merkel, P A, Nash, P, Opitz, C F, Pittrow, D, Rubin, L, Seibold, J R, Steen, V, Strand, C V, Tugwell, P S, Varga, J, Zink, A, and Furst, D E
- Abstract
There have been steady efforts to develop a combined response index for systemic sclerosis (CRISS). A parallel and equally successful effort has been made by an Expert Panel on Outcome Measures in PAH related to Systemic Sclerosis (EPOSS) to measure effect in treatment of pulmonary arterial hypertension of systemic sclerosis (PAH-SSc). CRISS conducted a Delphi process combined with expert review to identify 11 candidate domains for inclusion in a core set of outcomes for SSc clinical trials: soluble biomarkers, cardiac, digital ulcers, gastrointestinal, global health, health related quality of life (HRQOL) and function, musculoskeletal, pulmonary, Raynaud's, renal, and skin. Tools within domains were also agreed upon. Concentrating on one aspect of disease, PAH, EPOSS also conducted a Delphi process and judged the following domains as the most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure, cardiac function, exercise testing; severity of dyspnea, discontinuation of treatment; quality of life/activities of daily living; global state; and survival. Possible useful tools within each domain were also agreed on. Patient derived, physician derived, and objective measures of response will be included and combined with the idea that each reflects different aspects of PAH (EPOSS) and overall disease (CRISS) although this assumption may not prove true and can be separated if statistically and clinically valid to do so. In either case, prospective studies will require measurement of all domains, and tools are required and will be developed to define appropriate combined measures of response. CRISS and EPOSS are being developed through the OMERACT process. Through Delphi process and literature review significant progress has been made for both indices, and prospective data are being collected.
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- 2009
11. Abstract P2-10-28: The Prognostic Index, KiGE, Combining Proliferation, Histological Grade and Estrogen Receptor Status Challenges Gene Profiling – A Study in 1,854 Chemo-Naïve Women with N0/N1 Primary Breast Cancer.
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Strand, C, primary, Bak, M, additional, Borgquist, S, additional, Chebil, G, additional, Falck, A-K, additional, Fjällskog, M-L, additional, Grabau, D, additional, Hedenfalk, I, additional, Jirström, K, additional, Klintman, M, additional, Malmtröm, P, additional, Olsson, H, additional, Rydén, L, additional, Stål, O, additional, Bendahl, P-O, additional, and Fernö, M, additional
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- 2012
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12. Abstract P2-10-19: Are the mitotic factors Mitotic Activity Index (MAI) and Phosphohistone 3 (PPH3) stronger prognostic proliferation factors than Ki67 in node-negative breast cancer?
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Klintman, M, primary, Strand, C, additional, Gudlaugsson, E, additional, Janssen, E, additional, Skaland, I, additional, Malmström, P, additional, Baak, J, additional, and Fernö, M, additional
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- 2012
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13. Utilization of dried blood spots within drug discovery: modification of a standard DiLab® AccuSampler® to facilitate automatic dried blood spot sampling
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Clark, G T, primary, Giddens, G, additional, Burrows, L, additional, and Strand, C, additional
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- 2011
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14. Abstract P3-10-06: Modeling Prognostic Markers in Breast Cancer — Are We Using Them the Optimal Way?
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Strand, C, primary, Falck, A-K, additional, Jirström, K, additional, Malmström, P, additional, Rydén, L, additional, Bendahl, P-O, additional, and Fernö, M., additional
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- 2010
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15. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
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Windhagen, A, primary, Newcombe, J, additional, Dangond, F, additional, Strand, C, additional, Woodroofe, M N, additional, Cuzner, M L, additional, and Hafler, D A, additional
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- 1995
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16. Neural substrates of cognitive load changes during a motor task in subjects with stroke.
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Kimberley J, Lewis SM, Strand C, Rice BD, Hall S, and Slivnik P
- Abstract
Purpose: A critical component to rehabilitation is the degree to which we challenge patients to facilitate learning without providing excessive competition for cognitive resources. The purpose of this study was to examine brain activation and motor performance during changes in cognitive load in a continuous motor task in subjects with stroke (n = 7) and healthy subjects (n = 17).Methods: Subjects participated in a joystick drawing task during functional magnetic resonance imaging. Subjects attempted to continuously draw a square under three conditions of varying cognitive demands.Results: In subjects with stroke, results showed significantly less activation in contralateral primary motor area when the task did not require working memory demands and no change when the condition required online visual feedback processing. Bilaterally, the premotor cortex also demonstrated a significant decrease in activation when the task did not require working memory and then an increase in activation when online visual feedback processing was required. Despite these changes in activation, the accuracy of performance was maintained across the three conditions. Healthy subjects demonstrated no significant differences in activation between conditions.Conclusion: These data suggest that the sensorimotor areas investigated have the greatest demand when the task requires working memory, but that only the bilateral premotor area has increased demands when online visual feedback processing is required. Use of working memory and visual feedback should be carefully considered when designing rehabilitation programs to balance challenging patients with overwhelming their potentially limited cognitive resources. [ABSTRACT FROM AUTHOR]
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- 2008
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17. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndrome.
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Williams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, Revesz T, Williams, David R, Holton, Janice L, Strand, Catherine, Pittman, Alan, de Silva, Rohan, Lees, Andrew J, and Revesz, Tamas
- Abstract
Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF). Although pathological heterogeneity of progressive supranuclear palsy (PSP) has also been established, attempts to correlate this with clinical findings have only rarely provided conclusive results. The aim of this study was to investigate whether regional variations in the types of tau lesions or differences in overall tau load may explain the clinical differences between the RS, PSP-P and PAGF. Quantitative tau pathology assessment was performed in 17 brain regions in 42 cases of pathologically diagnosed PSP (22 RS, 14 PSP-P and 6 PAGF). Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology were quantitated and a grading system was developed separately for each region. Using these grades the overall tau load was calculated in each case. To establish a simplified system for grading the severity of tau pathology, all data were explored to identify the minimum number of regions that satisfactorily summarized the overall tau severity. The subthalamic nucleus, substantia nigra and globus pallidus were consistently the regions most severely affected by tau pathology. The mean severity in all regions of the RS group was higher than in PSP-P and PAGF, and the overall tau load was significantly higher in RS than in PSP-P (P = 0.002). Using only the grade of coiled body + thread lesions in the substantia nigra, caudate and dentate nucleus, a reliable and repeatable 12-tiered grading system was established (PSP-tau score: 0, mild tau pathology, restricted distribution; >7, severe, widespread tau pathology). PSP-tau score was negatively correlated with disease duration (Spearman's rho -0.36, P = 0.028) and time from disease onset to first fall (Spearman's rho -0.49, P = 0.003). The PSP-tau score in PSP-P (median 3, range 0-5) was significantly lower than in RS (median 5, range 2-10, Mann-Whitney U, P < 0.001). The two cases carrying the tau-H2 protective allele had the two lowest PSP-tau scores. We have identified significant pathological differences between the major clinical syndromes associated with PSP-tau pathology and the restricted, mild tau pathology in PSP-P supports its clinical distinction from RS. The grading system we have developed provides an easy-to-use and sensitive tool for the morphological assessment of PSP-tau pathology and allows for consideration of the clinical diversity that is known to occur in PSP. [ABSTRACT FROM AUTHOR]
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- 2007
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18. Antibody to cytomegalovirus in patients with sjögren's syndrome. As determined by an enzyme-linked immunosorbent assay.
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Shillitoe, Edward J., Daniels, Troy E., Whitcher, John P., Strand, C. Vibeke, Talal, Norman, and Greenspan, John S.
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- 1982
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19. A Science of Honesty?
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Strand, C. Lyle, primary
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- 1975
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20. Detection of Streptococcus pneumoniae in lower respiratory tract specimens by anaerobic culture technique
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Baesman, R K, primary and Strand, C L, additional
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- 1984
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21. Are the mitotic factors Mitotic Activity Index (MAI) and Phosphohistone 3 (PPH3) stronger prognostic proliferation factors than Ki67 in node-negative breast cancer?
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Klintman, M., Strand, C., Gudlaugsson, E., Janssen, E., Skaland, I., Malmström, P., Baak, J., and Fernö, M.
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- *
BREAST cancer research , *GENE expression , *GENETICS , *MITOSIS , *MICROARRAY technology - Abstract
Background: The prognostic value of proliferation in node-negative breast cancer, either in the form of Ki67 or as the main common denominator in different gene expression profiles, has become clearer over the last years. The St Gallen guidelines recommend the use of Ki67 to distinguish between the luminal A and luminal B-like subtypes. Also, data have shown that Ki67 can separate patients with histological grade 2 into two groups with significant difference in prognosis. However, there is no consensus on the methodology for Ki67, and genetic profiling is still expensive. Previous studies have shown a strong prognostic value of the mitosis- and late G2-specific proliferation factors Phosphohistone H3 (PPH3) and mitotic activity index (MAI) in node-negative breast cancer. The present study was set up to study the value of these two factors compared to Ki67, alone and combined. Material and methods: In 221 consecutive premenopausal node-negative breast cancer patients, of whom 87% had received no adjuvant medical treatment, PPH3 was assessed on tissue microarray (TMA), and MAI on whole sections. TMA-data on Ki67 was already available. Cut-offs for MAI, PPH3, and Ki67 were predefined. Cox proportional hazards regression was used to model the impact of the prognostic factors on distant disease-free survival (DDFS). The follow-up was restricted to the first 5 years after diagnosis, a time period during which 34 patients developed distant recurrences. Results: In univariate analysis the strongest prognostic proliferation factor for DDFS was MAI (HR 5.1 95%CI 2.4-11, p < 0.0001), followed by PPH3 (HR 3.7 95%CI 1.8-7.5, p < 0.0001), and Ki67 (HR 2.7 95%CI 1.3-5.4, p = 0.005). ER, PR, HER2, histological grade, and age were also significant prognostic factors. When adding PPH3 to MAI, the prognostic value of MAI was strengthened (HR 6.3 95%CI 2.6-15, p < 0.0001). This corresponded to a 5-year DDFS of 95% for the 57% of the patients who were low risk (95%CI 88-98%), and 71% (95%CI 60-80%) for the 43% high risk patients. Ki67 did however not add any prognostic value to MAI. When stratifying for ER status and histological grade, MAI was a significant prognostic factor in the ER+ patients (HR 15 95%CI 5.1-41, p < 0.0001), as well as in patients with histological grade 2 (HR 11 95%CI 3.2-38, p < 0.0001). In multivariate analysis including HER2, age, and ER, and one proliferation factor at a time, MAI was the only proliferation factor that added independent prognostic value (HR 3.6 95%CI 1.1-11, p = 0.028). Discussion: The present study on node-negative breast cancer patients confirms the strong prognostic value of the proliferation factors MAI and PPH3, in all patients, and more specifically in ER+ patients, and patients with histological grade 2. The study also suggests that by combining two proliferation factors, MAI and PPH3, an even stronger prognostic value is found. Ki67 however, did not add any prognostic value to MAI. Taken together, MAI and PPH3, alone and in combination may be helpful for prognostic considerations and for selection of adjuvant medical treatment. [ABSTRACT FROM AUTHOR]
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- 2012
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22. Gonococcal ophthalmia neonatorum after delivery by cesarean section: report of a case.
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Strand, Calvin L, Arango, Virgilio A., Strand, C L, and Arango, V A
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- 1979
23. The Prognostic Index, KiGE, Combining Proliferation, Histological Grade and Estrogen Receptor Status Challenges Gene Profiling -- A Study in 1,854 Chemo-Naïve Women with N0/N1 Primary Breast Cancer.
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Strand, C., Bak, M., Borgquist, S., Chebil, G., Falck, A.-K., Fjällskog, M.-L., Grabau, D., Hedenfalk, I., Jirström, K., Klintman, M., Malmtröm, P., Olsson, H., Rydén, L., Stål, O., Bendahl, P.-O., and Ferno, M.
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- *
ESTROGEN receptors , *BREAST cancer patients , *CYCLINS , *HISTOLOGY , *MULTIVARIATE analysis , *DRUG therapy - Abstract
Purpose: The aim was to validate the prognostic value of a previously defined index (CAGE), combining proliferation (Cyclin A), histological grade, and estrogen receptor (ER) in different subsets of primary breast cancer patients. In the present study, Ki67 was included in the index (KiGE) instead of cyclin A, since it is the generally accepted proliferation marker in clinical routine. Patients and methods: 1,854 chemo-naive patients with primary breast cancer were included. The low KiGE group consisted of histological grade 1 cases and grade 2 cases which were ER-positive and had low Ki67 expression. High KiGE consisted of all other cases. Results: The KiGE index separated patients into groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001). Conclusion: We have validated a prognostic index based on proliferation (Ki67), histological grade and ER, for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided. The KiGE index, based on clinically used factors, may challenge the more expensive gene expression profiles. [ABSTRACT FROM AUTHOR]
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- 2012
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24. Supplementary instructions and specifications for preparation of overbore fuel, PT-IP-381-A-FP
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Strand, C
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- 1962
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25. Fabrication of hot die sized Diffusion Bonded Fuel Elements for Supplement ``A`` to Production Test IP-546-A
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Strand, C
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- 1964
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26. Fabrication of hot die sized diffusion bonded fuel elements from oil and water quenched cores for production test IP-708-A
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Strand, C
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- 1964
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27. High-silicon aluminum cladding for hot die sized fuel elements: Interim report
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Strand, C
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- 1964
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28. Optimum canning conditions for four-inch I & E fuel elements
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Strand, C
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- 1960
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29. Status of development work on the hot die size fuel element growth problem
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Strand, C
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- 1964
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30. Fabrication of enriched hot die sized diffusion bonded fuel elements for Production Test IP-616-A
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Strand, C
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- 1964
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31. Effect of increased nickel content in canning baths
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Strand, C
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- 1960
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32. Interim report on hot die sizing variables test
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Strand, C
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- 1963
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33. Measurement of fuel element bond strength
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Strand, C
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- 1960
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34. Fabrication of hot die size diffusion bonded fuel elements for Production Test IP-546-A
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Strand, C
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- 1963
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35. End closure of hot die size diffusion bonded fuel elements
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Strand, C
- Published
- 1964
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36. A next-generation, histological atlas of the human brain and its application to automated brain MRI segmentation.
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Casamitjana A, Mancini M, Robinson E, Peter L, Annunziata R, Althonayan J, Crampsie S, Blackburn E, Billot B, Atzeni A, Puonti O, Balbastre Y, Schmidt P, Hughes J, Augustinack JC, Edlow BL, Zöllei L, Thomas DL, Kliemann D, Bocchetta M, Strand C, Holton JL, Jaunmuktane Z, and Iglesias JE
- Abstract
Magnetic resonance imaging (MRI) is the standard tool to image the human brain in vivo. In this domain, digital brain atlases are essential for subject-specific segmentation of anatomical regions of interest (ROIs) and spatial comparison of neuroanatomy from different subjects in a common coordinate frame. High-resolution, digital atlases derived from histology (e.g., Allen atlas [7], BigBrain [13], Julich [15]), are currently the state of the art and provide exquisite 3D cytoarchitectural maps, but lack probabilistic labels throughout the whole brain. Here we present NextBrain, a next-generation probabilistic atlas of human brain anatomy built from serial 3D histology and corresponding highly granular delineations of five whole brain hemispheres. We developed AI techniques to align and reconstruct ~10,000 histological sections into coherent 3D volumes with joint geometric constraints (no overlap or gaps between sections), as well as to semi-automatically trace the boundaries of 333 distinct anatomical ROIs on all these sections. Comprehensive delineation on multiple cases enabled us to build the first probabilistic histological atlas of the whole human brain. Further, we created a companion Bayesian tool for automated segmentation of the 333 ROIs in any in vivo or ex vivo brain MRI scan using the NextBrain atlas. We showcase two applications of the atlas: automated segmentation of ultra-high-resolution ex vivo MRI and volumetric analysis of Alzheimer's disease and healthy brain ageing based on ~4,000 publicly available in vivo MRI scans. We publicly release: the raw and aligned data (including an online visualisation tool); the probabilistic atlas; the segmentation tool; and ground truth delineations for a 100 μm isotropic ex vivo hemisphere (that we use for quantitative evaluation of our segmentation method in this paper). By enabling researchers worldwide to analyse brain MRI scans at a superior level of granularity without manual effort or highly specific neuroanatomical knowledge, NextBrain holds promise to increase the specificity of MRI findings and ultimately accelerate our quest to understand the human brain in health and disease., Competing Interests: Competing interests The authors have no relevant financial or non-financial interests to disclose.
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- 2024
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37. Author Correction: Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.
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Altay MF, Kumar ST, Burtscher J, Jagannath S, Strand C, Miki Y, Parkkinen L, Holton JL, and Lashuel HA
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- 2024
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38. Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.
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Altay MF, Kumar ST, Burtscher J, Jagannath S, Strand C, Miki Y, Parkkinen L, Holton JL, and Lashuel HA
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The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance among these disorders. Relying on antibodies that have not been assessed for their ability to detect the diverse forms of aSyn may lead to inaccurate estimations of aSyn pathology in human brains or disease models. To address this challenge, we developed and characterized an expanded antibody panel that targets different sequences and post-translational modifications along the length of aSyn, and that recognizes all monomeric, oligomeric, and fibrillar aSyn conformations. Next, we profiled aSyn pathology across sporadic and familial Lewy body diseases (LBDs) and reveal heterogeneous forms of aSyn pathology, rich in Serine 129 phosphorylation, Tyrosine 39 nitration and N- and C-terminal tyrosine phosphorylations, scattered both to neurons and glia. In addition, we show that aSyn can become hyperphosphorylated during processes of aggregation and inclusion maturation in neuronal and animal models of aSyn seeding and spreading. The validation pipeline we describe for these antibodies paves the way for systematic investigations into aSyn pathological diversity in the human brain, peripheral tissues, as well as in cellular and animal models of synucleinopathies., (© 2023. The Author(s).)
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- 2023
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39. Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma.
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Schoen RE, Boardman LA, Cruz-Correa M, Bansal A, Kastenberg D, Hur C, Dzubinski L, Kaufman SF, Rodriguez LM, Richmond E, Umar A, Szabo E, Salazar A, McKolanis J, Beatty P, Pai RK, Singhi AD, Jacqueline CM, Bao R, Diergaarde B, McMurray RP, Strand C, Foster NR, Zahrieh DM, Limburg PJ, and Finn OJ
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- Adult, Aged, Humans, Middle Aged, Immunoglobulin G, Vaccines, Subunit, Adenoma prevention & control, Colonic Neoplasms, Colorectal Neoplasms prevention & control
- Abstract
Purpose: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation., Patients and Methods: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0., Results: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events., Conclusions: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection., (©2023 American Association for Cancer Research.)
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- 2023
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40. Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy.
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Sonustun B, Altay MF, Strand C, Ebanks K, Hondhamuni G, Warner TT, Lashuel HA, and Bandopadhyay R
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- Antibodies, Humans, Inclusion Bodies, Lewy Bodies, Multiple System Atrophy pathology, Parkinson Disease pathology, alpha-Synuclein metabolism
- Abstract
Aggregated alpha-synuclein (α-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of α-synuclein exist, including phosphorylated and nitrated forms. It is unclear which α-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant α-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three α-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 IPD cases, 5 MSA cases, and 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 α-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 α-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 α-synuclein in MSA. Quantification of the LB scores revealed that pS129 α-synuclein was the dominant and earliest α-synuclein PTM, followed by nY39 α-synuclein, while lower amounts of pSer87 α-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.
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- 2022
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41. Optimization of AsCas12a for combinatorial genetic screens in human cells.
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DeWeirdt PC, Sanson KR, Sangree AK, Hegde M, Hanna RE, Feeley MN, Griffith AL, Teng T, Borys SM, Strand C, Joung JK, Kleinstiver BP, Pan X, Huang A, and Doench JG
- Subjects
- Acidaminococcus genetics, Apoptosis genetics, CRISPR-Associated Protein 9, Cell Line, Tumor, Gene Library, HEK293 Cells, Humans, RNA, Guide, CRISPR-Cas Systems, Bacterial Proteins genetics, Bacterial Proteins metabolism, CRISPR-Associated Proteins genetics, CRISPR-Associated Proteins metabolism, CRISPR-Cas Systems genetics, Endodeoxyribonucleases genetics, Endodeoxyribonucleases metabolism, Gene Editing methods
- Abstract
Cas12a RNA-guided endonucleases are promising tools for multiplexed genetic perturbations because they can process multiple guide RNAs expressed as a single transcript, and subsequently cleave target DNA. However, their widespread adoption has lagged behind Cas9-based strategies due to low activity and the lack of a well-validated pooled screening toolkit. In the present study, we describe the optimization of enhanced Cas12a from Acidaminococcus (enAsCas12a) for pooled, combinatorial genetic screens in human cells. By assaying the activity of thousands of guides, we refine on-target design rules and develop a comprehensive set of off-target rules to predict and exclude promiscuous guides. We also identify 38 direct repeat variants that can substitute for the wild-type sequence. We validate our optimized AsCas12a toolkit by screening for synthetic lethalities in OVCAR8 and A375 cancer cells, discovering an interaction between MARCH5 and WSB2. Finally, we show that enAsCas12a delivers similar performance to Cas9 in genome-wide dropout screens but at greatly reduced library size, which will facilitate screens in challenging models.
- Published
- 2021
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42. Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration.
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Woollacott IOC, Toomey CE, Strand C, Courtney R, Benson BC, Rohrer JD, and Lashley T
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- Adult, Aged, Female, Frontal Lobe metabolism, Frontotemporal Lobar Degeneration metabolism, Gray Matter metabolism, Humans, Immunohistochemistry, Male, Microglia metabolism, Middle Aged, Temporal Lobe metabolism, White Matter metabolism, tau Proteins metabolism, Frontal Lobe pathology, Frontotemporal Lobar Degeneration pathology, Gray Matter pathology, Microglia pathology, Temporal Lobe pathology, White Matter pathology
- Abstract
Background: Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer's disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy in sporadic and genetic FTLD, sporadic AD and controls., Methods: Immunohistochemistry was performed in frontal and temporal grey and white matter from 50 pathologically confirmed FTLD cases (31 sporadic, 19 genetic: 20 FTLD-tau, 26 FTLD-TDP, four FTLD-FUS), five AD cases and five controls, using markers to detect phagocytic (CD68-positive) and antigen-presenting (CR3/43-positive) microglia, and microglia in general (Iba1-positive). Microglial burden and activation (morphology) were assessed quantitatively for each microglial phenotype. Iba1-positive microglia were assessed semi-quantitatively for dystrophy severity and qualitatively for rod-shaped and hypertrophic morphology. Microglia were compared in each region between FTLD, AD and controls, and between different pathological subtypes of FTLD, including its main subtypes (FTLD-tau, FTLD-TDP, FTLD-FUS), and subtypes of FTLD-tau, FTLD-TDP and genetic FTLD. Microglia were also compared between grey and white matter within each lobe for each group., Results: There was a higher burden of phagocytic and antigen-presenting microglia in FTLD and AD cases than controls, but activation was often not increased. Burden was generally higher in white matter than grey matter, but activation was greater in grey matter. However, microglia varied regionally according to FTLD subtype and disease mechanism. Dystrophy was more severe in FTLD and AD than controls, and more severe in white than grey matter, but this also varied regionally and was particularly extensive in FTLD due to progranulin (GRN) mutations. Presence of rod-shaped and hypertrophic microglia also varied by FTLD subtype., Conclusions: This study demonstrates regionally variable microglial involvement in FTLD and links this to underlying disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.
- Published
- 2020
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43. Genetic screens in isogenic mammalian cell lines without single cell cloning.
- Author
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DeWeirdt PC, Sangree AK, Hanna RE, Sanson KR, Hegde M, Strand C, Persky NS, and Doench JG
- Subjects
- Apoptosis genetics, CRISPR-Cas Systems, Cell Line, Clone Cells, Gene Knockout Techniques, Gene Library, Gene Regulatory Networks, Humans, Multigene Family, Myeloid Cell Leukemia Sequence 1 Protein antagonists & inhibitors, Myeloid Cell Leukemia Sequence 1 Protein deficiency, Myeloid Cell Leukemia Sequence 1 Protein genetics, Poly (ADP-Ribose) Polymerase-1 antagonists & inhibitors, Poly (ADP-Ribose) Polymerase-1 deficiency, Poly (ADP-Ribose) Polymerase-1 genetics, Single-Cell Analysis, bcl-X Protein antagonists & inhibitors, bcl-X Protein deficiency, bcl-X Protein genetics, Genetic Testing methods
- Abstract
Isogenic pairs of cell lines, which differ by a single genetic modification, are powerful tools for understanding gene function. Generating such pairs of mammalian cells, however, is labor-intensive, time-consuming, and, in some cell types, essentially impossible. Here, we present an approach to create isogenic pairs of cells that avoids single cell cloning, and screen these pairs with genome-wide CRISPR-Cas9 libraries to generate genetic interaction maps. We query the anti-apoptotic genes BCL2L1 and MCL1, and the DNA damage repair gene PARP1, identifying both expected and uncharacterized buffering and synthetic lethal interactions. Additionally, we compare acute CRISPR-based knockout, single cell clones, and small-molecule inhibition. We observe that, while the approaches provide largely overlapping information, differences emerge, highlighting an important consideration when employing genetic screens to identify and characterize potential drug targets. We anticipate that this methodology will be broadly useful to comprehensively study gene function across many contexts.
- Published
- 2020
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44. Natural variation in C. elegans arsenic toxicity is explained by differences in branched chain amino acid metabolism.
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Zdraljevic S, Fox BW, Strand C, Panda O, Tenjo FJ, Brady SC, Crombie TA, Doench JG, Schroeder FC, and Andersen EC
- Subjects
- Animals, Caenorhabditis elegans enzymology, Genetic Variation, HEK293 Cells, Humans, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) metabolism, Amino Acids, Branched-Chain metabolism, Arsenic toxicity, Biological Variation, Population, Caenorhabditis elegans drug effects, Caenorhabditis elegans metabolism
- Abstract
We find that variation in the dbt-1 gene underlies natural differences in Caenorhabditis elegans responses to the toxin arsenic. This gene encodes the E2 subunit of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component of branched-chain amino acid (BCAA) metabolism. We causally linked a non-synonymous variant in the conserved lipoyl domain of DBT-1 to differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate that differences in responses to arsenic are caused by variation in iso-branched chain fatty acids. Additionally, we show that levels of branched chain fatty acids in human cells are perturbed by arsenic treatment. This finding has broad implications for arsenic toxicity and for arsenic-focused chemotherapeutics across human populations. Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the power of C. elegans natural genetic diversity to identify novel mechanisms by which environmental toxins affect organismal physiology., Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)., Competing Interests: SZ, BF, CS, OP, FT, SB, TC, JD, FS, EA No competing interests declared, (© 2019, Zdraljevic et al.)
- Published
- 2019
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45. Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities.
- Author
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Sanson KR, Hanna RE, Hegde M, Donovan KF, Strand C, Sullender ME, Vaimberg EW, Goodale A, Root DE, Piccioni F, and Doench JG
- Subjects
- CRISPR-Associated Protein 9, Streptococcus pyogenes, CRISPR-Cas Systems, Genomic Library
- Abstract
The creation of genome-wide libraries for CRISPR knockout (CRISPRko), interference (CRISPRi), and activation (CRISPRa) has enabled the systematic interrogation of gene function. Here, we show that our recently-described CRISPRko library (Brunello) is more effective than previously published libraries at distinguishing essential and non-essential genes, providing approximately the same perturbation-level performance improvement over GeCKO libraries as GeCKO provided over RNAi. Additionally, we present genome-wide libraries for CRISPRi (Dolcetto) and CRISPRa (Calabrese), and show in negative selection screens that Dolcetto, with fewer sgRNAs per gene, outperforms existing CRISPRi libraries and achieves comparable performance to CRISPRko in detecting essential genes. We also perform positive selection CRISPRa screens and demonstrate that Calabrese outperforms the SAM approach at identifying vemurafenib resistance genes. We further compare CRISPRa to genome-scale libraries of open reading frames (ORFs). Together, these libraries represent a suite of genome-wide tools to efficiently interrogate gene function with multiple modalities.
- Published
- 2018
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46. Uncoupling of sgRNAs from their associated barcodes during PCR amplification of combinatorial CRISPR screens.
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Hegde M, Strand C, Hanna RE, and Doench JG
- Subjects
- Cell Line, Tumor, Genetic Vectors, Humans, Lentivirus genetics, Recombination, Genetic, CRISPR-Cas Systems, DNA Barcoding, Taxonomic methods, High-Throughput Nucleotide Sequencing methods, Polymerase Chain Reaction methods, RNA, Guide, CRISPR-Cas Systems genetics
- Abstract
Many implementations of pooled screens in mammalian cells rely on linking an element of interest to a barcode, with the latter subsequently quantitated by next generation sequencing. However, substantial uncoupling between these paired elements during lentiviral production has been reported, especially as the distance between elements increases. We detail that PCR amplification is another major source of uncoupling, and becomes more pronounced with increased amounts of DNA template molecules and PCR cycles. To lessen uncoupling in systems that use paired elements for detection, we recommend minimizing the distance between elements, using low and equal template DNA inputs for plasmid and genomic DNA during PCR, and minimizing the number of PCR cycles. We also present a vector design for conducting combinatorial CRISPR screens that enables accurate barcode-based detection with a single short sequencing read and minimal uncoupling., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
47. Orthologous CRISPR-Cas9 enzymes for combinatorial genetic screens.
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Najm FJ, Strand C, Donovan KF, Hegde M, Sanson KR, Vaimberg EW, Sullender ME, Hartenian E, Kalani Z, Fusi N, Listgarten J, Younger ST, Bernstein BE, Root DE, and Doench JG
- Subjects
- Apoptosis genetics, Gene Knockout Techniques, Gene Targeting, Humans, Machine Learning, Mitogen-Activated Protein Kinase Kinases genetics, Signal Transduction genetics, Staphylococcus aureus genetics, Streptococcus pyogenes genetics, Tumor Suppressor Protein p53 genetics, CRISPR-Cas Systems genetics, Epistasis, Genetic genetics, Genetic Testing, RNA, Guide, CRISPR-Cas Systems genetics
- Abstract
Combinatorial genetic screening using CRISPR-Cas9 is a useful approach to uncover redundant genes and to explore complex gene networks. However, current methods suffer from interference between the single-guide RNAs (sgRNAs) and from limited gene targeting activity. To increase the efficiency of combinatorial screening, we employ orthogonal Cas9 enzymes from Staphylococcus aureus and Streptococcus pyogenes. We used machine learning to establish S. aureus Cas9 sgRNA design rules and paired S. aureus Cas9 with S. pyogenes Cas9 to achieve dual targeting in a high fraction of cells. We also developed a lentiviral vector and cloning strategy to generate high-complexity pooled dual-knockout libraries to identify synthetic lethal and buffering gene pairs across multiple cell types, including MAPK pathway genes and apoptotic genes. Our orthologous approach also enabled a screen combining gene knockouts with transcriptional activation, which revealed genetic interactions with TP53. The "Big Papi" (paired aureus and pyogenes for interactions) approach described here will be widely applicable for the study of combinatorial phenotypes.
- Published
- 2018
- Full Text
- View/download PDF
48. Natural variation in a single amino acid substitution underlies physiological responses to topoisomerase II poisons.
- Author
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Zdraljevic S, Strand C, Seidel HS, Cook DE, Doench JG, and Andersen EC
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Caenorhabditis elegans drug effects, Caenorhabditis elegans genetics, DNA Damage drug effects, DNA-Binding Proteins antagonists & inhibitors, Humans, Saccharomyces cerevisiae genetics, Topoisomerase II Inhibitors administration & dosage, Amino Acid Substitution genetics, DNA Topoisomerases, Type II genetics, DNA-Binding Proteins genetics, Precision Medicine
- Abstract
Many chemotherapeutic drugs are differentially effective from one patient to the next. Understanding the causes of this variability is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate sensitivity to a group of anti-neoplastic drugs that target topoisomerase II using the model organism Caenorhabditis elegans. We show that wild strains of C. elegans vary in their sensitivity to these drugs, and we use an unbiased genetic approach to demonstrate that this natural variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and its poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPIIα and glutamine in hTOPIIβ). We go on to show that this amino acid difference between the two human topoisomerase isoforms influences cytotoxicity of topoisomerase II poisons in human cell lines. These results explain why hTOPIIα and hTOPIIβ are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses.
- Published
- 2017
- Full Text
- View/download PDF
49. 9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease.
- Author
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Massey LA, Miranda MA, Al-Helli O, Parkes HG, Thornton JS, So PW, White MJ, Mancini L, Strand C, Holton J, Lees AJ, Revesz T, and Yousry TA
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Aging pathology, Brain Diseases diagnostic imaging, Brain Diseases pathology, Magnetic Resonance Imaging methods, Substantia Nigra diagnostic imaging, Substantia Nigra pathology, Tissue Banks
- Abstract
Background: The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy., Methods: 23 brains were selected from the Queen Square Brain Bank (10 controls, 8 progressive supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4 Tesla spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue, Perls stain, and immunohistochemistry for substance P and calbindin. Once the anatomy was defined on histology the dimensions and volume of the substantia nigra were determined on high field magnetic resonance images., Results: The anterior border of the substantia nigra was defined by the crus cerebri. In the medial half it was less distinct due to the deposition of iron and the interdigitation of white matter and the substantia nigra. The posterior border was flanked by white matter bridging the red nucleus and substantia nigra and seen as hypointense on spin-echo magnetic resonance images. Within the substantia nigra high signal structures corresponded to confirmed nigrosomes. These were still evident in Parkinson's disease but not in progressive supranuclear palsy. The volume and dimensions of the substantia nigra were similar in Parkinson's disease and controls, but reduced in progressive supranuclear palsy., Conclusions: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.
- Published
- 2016
- Full Text
- View/download PDF
50. The prognostic value of mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A, and Ki67, alone and in combinations, in node-negative premenopausal breast cancer.
- Author
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Klintman M, Strand C, Ahlin C, Beglerbegovic S, Fjällskog ML, Grabau D, Gudlaugsson E, Janssen EA, Lövgren K, Skaland I, Bendahl PO, Malmström P, Baak JP, and Fernö M
- Subjects
- Breast Neoplasms metabolism, Cell Proliferation, Disease-Free Survival, Female, Humans, Multivariate Analysis, Phosphorylation, Prognosis, Receptors, Estrogen metabolism, Breast Neoplasms pathology, Cyclin A metabolism, Cyclin B1 metabolism, Histones metabolism, Ki-67 Antigen metabolism, Lymph Nodes pathology, Mitotic Index, Premenopause metabolism
- Abstract
Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off ≥10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95%CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95%CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95%CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95%CI: 1.1-6.7), and cyclin A (HR=2.7, 95%CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
- Published
- 2013
- Full Text
- View/download PDF
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