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204. Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development

Author

Reddy, Pradeep, Shen, Lijun, Ren, Chong, Boman, Karin, Lundin, Eva, Ottander, Ulrika, Lindgren, Peter, Liu, Yi-xun, Sun, Qing-yuan, and Liu, Kui

Subjects
Oocytes -- Research, Developmental biology -- Research, Embryonic stem cells -- Research, Biological sciences
Abstract

Although communications between mammalian oocytes and their surrounding granulosa cells mediated by the Kit--Kit ligand (KL, or stem cell factor, SCF) system have been proven to be crucial for follicular development, Kit downstream signaling pathways in mammalian oocytes are largely unknown. In this study, by using ovaries and isolated oocytes from postnatal mice and rats, we demonstrated for the first time that components of the PI3 kinase pathway, the serine/threonine kinase Akt (PKB) which enhances cellular proliferation and survival, and an Akt substrate FKHRL1 which is a transcription factor that leads to apoptosis and cell cycle arrest, are expressed in mammalian oocytes. By using an in vitro oocytes culture system, we found that oocytes-derived Akt and FKHRL1 are regulated by SCF. Treatment of cultured oocytes with SCF cannot only rapidly phosphorylate and activate Akt, but also simultaneously phosphorylate and may therefore functionally suppress FKHRL1, through the action of PI3 kinase. Together with our in situ hybridization and immunohistochemistry data that Akt and FKHRL1 are mostly expressed in oocytes in primordial and primary ovaries and reports that FKHRL1 gene-deficient mice exhibited excessive activation from primordial to primary follicles as well as enlarged oocyte sizes, we suppose that in mammalian oocytes, actions of granulosa cell derived SCF on primordial to primary follicle transition and subsequent follicle development may involve activation of Akt and inhibition of FKHRL1 activities in oocytes. The role of oocyte's Akt may be to enhance follicle development and the role of oocyte's FKHRL1 may be to inhibit follicle development. We propose that the cascade from granulosa cell SCF to oocyte Kit-PI3 kinase-Akt-FKHRL1 may play an important role to regulate the growth rate of mammalian oocytes and hypothetically also the oocyte secretion of factors that may regulate the activation and early development of ovarian follicles. Keywords: Mammalian oocytes; Stem cell factor (SCF); Kit; PI3 kinase; Akt; FKHRL1

Published
2005

215. Entangling Corporate Innovation, Systems Thinking and Design Thinking.

Author

Lynch, Matthew, Andersson, Gunnar, Johansen, Frode Ramstad, and Lindgren, Peter

Subjects
DESIGN thinking, SYSTEMS theory, ECO-labeling, ENVIRONMENTAL education, SERVER farms (Computer network management), TEACHING models, TEACHING methods, ACADEMIC-industrial collaboration
Abstract

The world faces an increasing number of environmental problems such as climate change, depletion of biodiversity, plastic pollution and the side effects of mining. In a world with so many environmental challenges creating additional consumer items, even when they are labelled environmentally friendly, can and does have environmental consequences. We suggest that design thinking can and should include a more holistic systems thinking perspective as part of its drive to encourage corporate innovation. We argue that design thinking should take a much wider view of who are their stakeholders. In order to demonstrate the connection between corporate innovation, systems thinking and design thinking, we draw on a case study regarding the creation of a new data center. The case demonstrates how design thinking with elements of system thinking can be used to generate solutions that has positive impacts for multiple stakeholders, including the environment. The case study demonstrates that these combined perspectives can also be used as a teaching model to shift students’ mindsets towards not just finding solutions that suit a customer or a project owner, but also the environment and other stakeholders. The case demonstrates that practical positive results can be generated over a short period of time, with little investment. The case also highlights a successful approach to industry/university collaborations. The research delves into the basics of systems thinking, and how there is a connection with design thinking. We then discuss the teaching methodology and approach to using design thinking/systems thinking to solve the case challenge. We then present the results of the challenge and the discussion regarding how such projects can play a role in shifting students’ mindset towards having a more environmentally friendly perspective while engaging in corporate innovation. [ABSTRACT FROM AUTHOR]

Published
2021
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216. Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden

Author

Landmesser, Ulf, primary, Lindgren, Peter, additional, Hagström, Emil, additional, van Hout, Ben, additional, Villa, Guillermo, additional, Pemberton-Ross, Peter, additional, Arellano, Jorge, additional, Svensson, Maria Eriksson, additional, Sibartie, Mahendra, additional, and Fonarow, Gregg C, additional

Published
2020
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218. Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study

Author

Bergman, Lina, primary, Sandström, Anna, additional, Jacobsson, Bo, additional, Hansson, Stefan, additional, Lindgren, Peter, additional, Larsson, Anders, additional, Imberg, Henrik, additional, Conner, Peter, additional, Kublickas, Marius, additional, Carlsson, Ylva, additional, and Wikström, Anna-Karin, additional

Published
2020
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220. A Swedish primary healthcare prevention programme focusing on promotion of physical activity and a healthy lifestyle reduced cardiovascular events and mortality: 22-year follow-up of 5761 study participants and a reference group

Author

Journath, Gunilla, primary, Hammar, Niklas, additional, Vikström, Max, additional, Linnersjö, Anette, additional, Walldius, Göran, additional, Krakau, Ingvar, additional, Lindgren, Peter, additional, de Faire, Ulf, additional, and Hellenius, Mai-Lis, additional

Published
2020
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229. The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Author

Buffin-Meyer, Bénédicte, Klein, Julie, van der Zanden, Loes F M, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Hindryckx, An, Wühl, Elke, Persico, Nicola, Oepkes, Dick, Schreuder, Michiel F, Tkaczyk, Marcin, Ariceta, Gema, Fossum, Magdalena, Parvex, Paloma, Feitz, Wout, Olsen, Henning, Montini, Giovanni, Decramer, Stéphane, Schanstra, Joost P, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnès, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, Demede, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Schaefer, Franz, Elsässer, Michael, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika A, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, van Scheltema, Phebe Adama, Kortmann, Barbara, Schreuder, Michiel, Stańczyk, Małgorzata, Szaflik, Krzysztof, Wojtera, Justyna, Krzeszowski, Waldemar, Talar, Tomasz, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Arevalo, Silvia, Rodo, Carlota, Lindgren, Peter, Chehade, Hassib, ANTENATAL Consortium, Hindryckx, A., De Catte, L., Vayssieres, C., Sartor, A., Groussolles, M., Plard, C., Guerby, P., Connan, L., Morin, M., Simon, E., Breaud, J., Saliou, A.H., De Parscau, L., Jay, N., Germouty, I., Le Bouar, G., Ryckewaert, A., Manca-Pellissier, M.C., Merrot, T., Laurichesse, H., Gallot, D., Bessenay, L., Bidat, L., Boize, P., Winer, N., Allain-Launey, E., Le Vaillant, C., Prieur, F., Lavocat, M.P., Coatleven, F., Debromez, E., Harembat, J., Llanas, B., Favre, R., Moog, R., Zaloszyc, A., Massardier, J., Demede, D., Perrotin, F., Cloarec, S., Vequeau-Goua, V., Descombes, E., Boulot, P., Morin, D., Fuchs, F., Tenenbaum, J., Ville, Y., Blanc, T., Heidet, L., Paris, A., Dobremez, E., Froute, M.F., Gondry, J., Muszynski, C., Haraux, E., Lobelle, F., Chevreau, J., Rosenblatt, J., Baudoin, V., Deschenes, G., Guigue, V., Amblard, F., Bourdat-Michel, G., Wühl, E., Schaefer, F., Elsässer, M., Persico, N., Rossi, F., Manzoni, G., De Marco, E.A., Montini, G., Capone, V., Caforio, L., Zaccara, A., Innocenzi, M., Bagolan, P., Capozza, N., Castagnetti, M., Mancini, M., Oepkes, D., van Scheltema, P.A., Feitz, W., Kortmann, B., Schreuder, M., Tkaczyk, M., Stańczyk, M., Szaflik, K., Wojtera, J., Krzeszowski, W., Talar, T., Pawłowska, B., Fortecka-Piestrzeniewicz, K., Olejniczak, D., Ariceta, G., Arevalo, S., Rodo, C., Fossum, M., Lindgren, P., Parvex, P., Chehade, H., Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Leiden University Medical Center (LUMC), Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Geneva University Hospital (HUG), Aarhus University Hospital, Aarhus University [Aarhus], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, ANTENATAL Consortium: An Hindryckx, Luc De Catte, Christophe Vayssieres, Agnès Sartor, Marion Groussolles, Christelle Plard, Paul Guerby, Laure Connan, Mathieu Morin, Elizabeth Simon, Jean Breaud, Anne-Hélène Saliou, Loic De Parscau, Nadine Jay, Isabelle Germouty, Gwenaelle Le Bouar, Amelie Ryckewaert, Marie-Christine Manca-Pellissier, Thierry Merrot, Helene Laurichesse, Denis Gallot, Lucie Bessenay, Laurent Bidat, Philippe Boize, Norbert Winer, Emma Allain-Launey, Claudine Le Vaillant, Fabienne Prieur, Marie-Pierre Lavocat, Frederic Coatleven, Eric Debromez, Jérôme Harembat, Brigitte Llanas, Romain Favre, Raphael Moog, Ariane Zaloszyc, Jérôme Massardier, Delphine Demede, Franck Perrotin, Sylvie Cloarec, Valérie Vequeau-Goua, Emmanuelle Descombes, Pierre Boulot, Denis Morin, Florent Fuchs, Julie Tenenbaum, Yves Ville, Thomas Blanc, Laurence Heidet, Anne Paris, Eric Dobremez, Marie-Françoise Froute, Jean Gondry, Charles Muszynski, Elodie Haraux, Fabienne Lobelle, Julien Chevreau, Jonathan Rosenblatt, Véronique Baudoin, Georges Deschenes, Virginie Guigue, Florence Amblard, Guylhène Bourdat-Michel, Elke Wühl, Franz Schaefer, Michael Elsässer, Nicola Persico, Federica Rossi, Gianantonio Manzoni, Erika A De Marco, Giovanni Montini, Valentina Capone, Leonardo Caforio, Antonio Zaccara, Michele Innocenzi, Pietro Bagolan, Nicola Capozza, Marco Castagnetti, Mariangela Mancini, Dick Oepkes, Phebe Adama van Scheltema, Wout Feitz, Barbara Kortmann, Michiel Schreuder, Marcin Tkaczyk, Małgorzata Stańczyk, Krzysztof Szaflik, Justyna Wojtera, Waldemar Krzeszowski, Tomasz Talar, Barbara Pawłowska, Katarzyna Fortecka-Piestrzeniewicz, Dariusz Olejniczak, Gema Ariceta, Silvia Arevalo, Carlota Rodo, Magdalena Fossum, Peter Lindgren, Paloma Parvex, Hassib Chehade., Schanstra, Joost, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Università degli Studi di Milano = University of Milan (UNIMI)

Subjects
Posterior urethral valve, medicine.medical_specialty, Urinary system, [SDV]Life Sciences [q-bio], kidney disease, prenatal biomarkers, Renal function, Prenatal care, 030204 cardiovascular system & hematology, DIAGNOSIS, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Medicine, obstructive uropathy, Obstructive uropathy, development, 030304 developmental biology, RISK, 0303 health sciences, Transplantation, Kidney, ddc:618, Science & Technology, business.industry, Obstetrics, Original Articles, prediction, Urology & Nephrology, Omics, medicine.disease, 6. Clean water, 3. Good health, [SDV] Life Sciences [q-bio], Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], medicine.anatomical_structure, Nephrology, embryonic structures, Settore MED/20, URINARY-TRACT OBSTRUCTION, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Life Sciences & Biomedicine, Kidney disease
Abstract

Altres ajuts: The study is partially made possible by support of the 'Programme Hospitalier de Recherche Clinique and 'La Foundation de la Recherche Médicale (grant number DEQ20170336759, France). M.T. was supported by the Polish Mothers Memorial Hospital Research Institute (internal grant number 2016/IV/54-GW. LvdZ is supported by a Kolff grant from the Dutch Kidney Foundation (13OKJ36) and a ZonMW-VENI grant from the Netherlands Organisation for Scientific Research (91618036). This project has been supported by ERN ERKNet and ERN eUROGEN, which are partly co-funded by the European Union within the framework of the Third Health Programme 'ERN-2016-Framework Partnership Agreement 2017-2021'. Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.

Published
2020
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233. Blockade of the kallikrein-kinin system reduces endothelial complement activation in vascular inflammation

Author

Davalieva, Katarina, Makridakis, Manousos, Vlahou, Antonia, Frantzi, Maria, Boizard, Franck, Moussaoui, Nabila, Lescat, Ophélie, Fedou, Camille, Feuillet, Guylène, Casemayou, Audrey, Neau, Eric, Decatte, Luc, Raaijmakers, Anke, Vayssière, Christophe, Goua, Valérie, Lucas, Charlotte, Benachi, Alexandra, Delmas, Hélène Laurichesse, Allain-Launay, Emma, Boudailliez, Bernard, Simon, Elisabeth, Noel, Catherine, Floch, Corinne, Bourdat-Michel, Guylène, Weingertner, Anne-Sophie, Oury, Jean-François, Baudouin, Véronique, Bory, Jean-Paul, Pietrement, Christine, Fiorenza, Maryse, Kessler, Sylvie, Auriol, Françoise Conte, Marcorelles, Pascale, Collardeau-Frachon, Sophie, Magalhães, Pedro, Batut, Julie, Blader, Patrick, Saulnier Blache, Jean-Sebastien, Allegaert, Karel, Aubard, Yves, Basmaison, Odile, Benevent, Jean-Baptiste, Biquard, Florence, Champion, Gérard, Delbosc, Jean-Marie, Eckart, Philippe, Gaucherand, Pascal, Guigonis, Vincent, Hougas, Blandine, Martin, Alain, Martin, Sophie, Maupin-Hyvonnet, Mariannick, Merveille, Marina, Mousty, Eve, Nobili, François, Taque, Sophie, Latosinska, Agnieszka, Faguer, Stanislas, Beige, Joachim, van der Zanden, Loes, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Olsen, Henning, Hindryckx, An, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnes, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, DEMEDE, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Wühl, Elke, Schaefer, Franz, Elsässer, Michael, Persico, Nicola, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika, Montini, Giovanni, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, Oepkes, Dick, van Scheltema, Phebe Adama, Feitz, Wout, Kortmann, Barbara, Schreuder, Michiel, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Ariceta, Gema, Arevalo, Silvia, RODO, Carlota, Fossum, Magdalena, Lindgren, Peter, Parvex, Paloma, Chehade, Hassib, He, Tianlin, Metzger, Jochen, Mullen, William, Mischak, Harald, Zürbig, Petra, Jankowski, Vera, Buffin-Meyer, Bénédicte, Tkaczyk, Marcin, Stańczyk, Małgorzata, Breuil, Benjamin, Siwy, Justyna, Szaflik, Krzysztof, Talar, Tomasz, Wojtera, Justyna, Krzeszowski, Waldemar, Decramer, Stéphane, Lopatko Fagerström, Ingrid, Ståhl, Anne-lie, Mossberg, Maria, Tati, Ramesh, Kristoffersson, Ann-Charlotte, Kahn, Robin, Bascands, Jean-Loup, Klein, Julie, Schanstra, Joost, Segelmark, Mårten, Karpman, Diana, Department of Pediatrics [Lund, Sweden] (Clinical Sciences), Lund University [Lund], Wallenberg Center for Molecular Medicine [Lund, Sweden], Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Nephrology [Lund, Sweden] (Clinical Sciences Lund), Department of Medical and Health Sciences [Lund, Sweden], Linköping University (LIU), The study was supported by The Swedish Research Council (K2015-99X-22877-01-6 and 2017-01920), The Knut and Alice Wallenberg Foundation (Wallenberg Clinical Scholar 2015.0320), The Torsten Söderberg Foundation, Skåne Centre of Excellence in Health, IngaBritt och Arne Lundberg's Research Foundation, Crown Princess Lovisa's Society for Child Care, Region Skåne and The Konung Gustaf V:s 80-årsfond (all to DK). Alfred Österlund Foundation (to LMFLL and RK). TheWallenberg Center forMolecular Medicine, The Swedish RheumatismAssociation, The Anna-Greta Crafoord Foundation, Greta and Johan Kock's Foundation, the Samariten Foundation, Fanny Ekdahl foundation, the Jerring foundation and the Thelma Zoegas Foundation (to RK). JPS and JK were partially funded by a grant from the 'Fondation pour la Recherche Médicale' (grant number DEQ20170336759). MS was funded by The Swedish Rheumatism Association and the Ingrid Asp Foundation., Schanstra, Joost, Macedonian Academy of Sciences and Arts [Skopje, North Macedonia] (MASA), Biomedical Research Foundation of the Academy of Athens (BRFAA), Mosaiques Diagnostics & Therapeutics (MOSAIQUES DIAGNOSTICS & THERAPEUTICS), Mosaiques Diagnostics & Therapeutics AG, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], KfH-Nierenzentrum und Klinikum St. Georg, Nephrologie, Leipzig, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Mosaiques Diagnostics GmbH [Hanovre, Allemagne], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Mosaiques Diagnostics GmbH [Hannover, Germany], Mosaiques Diagnostics and Therapeutics AG [Hannover, Germany], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, Male, Research paper, Mouse, Kallikrein-Kinin System, [SDV]Life Sciences [q-bio], Pharmacology, Kidney, Mice, 0302 clinical medicine, Glomerular C3 deposition, Cell-Derived Microparticles, Complement Activation, Cells, Cultured, Chemistry, General Medicine, Kinin, Middle Aged, Receptor antagonist, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, medicine.symptom, Endothelial microvesicles, Complement C1 Inhibitor Protein, Protein Binding, Vasculitis, Complement, Radiology, Nuclear Medicine and Medical Imaging, Adult, Endothelium, medicine.drug_class, Inflammation, Bradykinin, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Classical complement pathway, medicine, Animals, Humans, Aged, Endothelial Cells, Biological Transport, Complement System Proteins, Microvesicles, Complement system, Disease Models, Animal, 030104 developmental biology, Immunoglobulin G, Endothelium, Vascular, Radiologi och bildbehandling
Abstract

Background: The complement and kallikrein-kinin systems (KKS) are activated during vascular inflammation. The aim of this study was to investigate if blockade of the KKS can affect complement activation on the endothelium during inflammation. Methods: Complement deposition on endothelial microvesicles was assayed in vasculitis patient plasma samples and controls. Plasma was perfused over glomerular endothelial cells and complement deposition assayed by flow cytometry. The effect of the kinin system was assessed using kinin receptor antagonists and C1-inhibitor. The in vivo effect was assessed in kidney sections from mice with nephrotoxic serum-induced glomerulonephritis treated with a kinin receptor antagonist. Findings: Vasculitis patient plasma had significantly more C3- and C9-positive endothelial microvesicles than controls. Perfusion of patient acute-phase plasma samples over glomerular endothelial cells induced the release of significantly more complement-positive microvesicles, in comparison to remission or control plasma. Complement activation on endothelial microvesicles was reduced by kinin B1- and B2-receptor antagonists or by C1-inhibitor (the main inhibitor of the classical pathway and the KKS). Likewise, perfusion of glomerular endothelial cells with C1-inhibitor-depleted plasma induced the release of complement-positive microvesicles, which was significantly reduced by kinin-receptor antagonists or C1-inhibitor. Mice with nephrotoxic serum-induced glomerulonephritis exhibited significantly reduced glomerular C3 deposition when treated with a B1-receptor antagonist. Interpretation: Excessive complement deposition on the endothelium will promote endothelial injury and the release of endothelial microvesicles. This study demonstrates that blockade of the KKS can reduce complement activation and thereby the inflammatory response on the endothelium. (C) 2019 The Authors. Published by Elsevier B.V. Funding Agencies|Swedish Research CouncilSwedish Research Council [K2015-99X-22877-01-6, 2017-01920]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2015.0320]; Torsten Soderberg Foundation; Skane Centre of Excellence in Health; Crown Princess Lovisas Society for Child Care; Konung Gustaf V:s 80-arsfond; Alfred Osterlund Foundation; Wallenberg Center for Molecular Medicine; Swedish Rheumatism Association; Anna-Greta Crafoord Foundation; Greta and Johan Kocks Foundation; Samariten Foundation; Fanny Ekdahl foundation; Jerring foundation; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale [DEQ20170336759]; Ingrid Asp Foundation; IngaBritt och Arne Lundbergs Research Foundation; Region Skane; Thelma Zoegas Foundation

Published
2019
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235. Business Model Innovation Process Management in a Business Model Innovation Continuum

Author

Andersen, Gitte Kingo, Lindgren, Peter, and Flarup, Jane

Subjects
), Process and role(s) of Process Manager in BMI, Process Management BMI competencies, BM three-dimensional continuum, Different roles and positions in Process Management of BMI, Process Management of Business Model Innovation (BMI), Business Process Management, The Process Manager in the Business Model Innovation Lab
Abstract

It is our hypothesis but also our experience from a numerous Business Model Innovation processes that it is crucial to focus on the importance of facilitating the participants, students or Businesses, when doing Business Model Innovation projects in accordance with the Multi Business Model Innovation concept developed by Professor Lindgren. This paper describes our preliminary research process’s and results regarding: What kind of activities seems to be necessary by the Multi Business Model Innovation Process Manager when facilitating participants social and collaborative teamwork processes doing Multi Business Model Innovation in a special designed business room, the B-Lab? Our research seems to show that the Multi Business Model Innovation Process Management takes place in a 3D continuum with different phases, roles and processes. In here the Process Manager must handle different theoretical and practical necessary knowledge and experience about the concept curriculum, the tools, the Multi Business Model Innovation dimensions and activities during the: Introduction, Downloading, Seeing, Sensing and Pitch phases plus know how to facilitate participants (students’ or business’s) teamwork when doing Business Model Innovation in the B-Lab. The Process Manager must be very flexible and master several roles and perspectives switching from position to position and from subject to subject in a short time, not in a linear continuum over time, but forward and reverse from giving the answers to ask the questions. Therefore, we continue our research with a larger cohort of participants and B-labs to develop a Process Manager Framework in doing Business Model Innovation processes.

Published
2019

237. †Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)

Author

Rydén, Lars, Standl, Eberhard, Bartnik, Małgorzata, Van den Berghe, Greet, Betteridge, John, de Boer, Menko-Jan, Cosentino, Francesco, Jönsson, Bengt, Laakso, Markku, Malmberg, Klas, Priori, Silvia, Östergren, Jan, Tuomilehto, Jaakko, Thrainsdottir, Inga, Vanhorebeek, Ilse, Stramba-Badiale, Marco, Lindgren, Peter, Qiao, Qing, Priori, Silvia G., Blanc, Jean-Jacques, Budaj, Andrzej, Camm, John, Dean, Veronica, Deckers, Jaap, Dickstein, Kenneth, Lekakis, John, McGregor, Keith, Metra, Marco, Morais, João, Osterspey, Ady, Tamargo, Juan, Zamorano, José Luis, Deckers, Jaap W., Bertrand, Michel, Charbonnel, Bernard, Erdmann, Erland, Ferrannini, Ele, Flyvbjerg, Allan, Gohlke, Helmut, Juanatey, Jose Ramon Gonzalez, Graham, Ian, Monteiro, Pedro Filipe, Parhofer, Klaus, Pyörälä, Kalevi, Raz, Itamar, Schernthaner, Guntram, Volpe, Massimo, and Wood, David

Published
2007

239. Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT) : a study protocol for a Swedish prospective multicentre cohort study

Author

Bergman, Lina, Sandström, Anna, Jacobsson, Bo, Hansson, Stefan, Lindgren, Peter, Larsson, Anders, Imberg, Henrik, Conner, Peter, Kublickas, Marius, Carlsson, Ylva, Wikström, Anna-Karin, Bergman, Lina, Sandström, Anna, Jacobsson, Bo, Hansson, Stefan, Lindgren, Peter, Larsson, Anders, Imberg, Henrik, Conner, Peter, Kublickas, Marius, Carlsson, Ylva, and Wikström, Anna-Karin

Abstract

INTRODUCTION: First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. METHODS AND ANALYSIS: This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. ETHICS AND DISSEMINATION: Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed

Published
2020
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240. Second trimester cervical length measurements with transvaginal ultrasound : A prospective observational agreement and reliability study

Author

Kuusela, Pihla, Wennerholm, Ulla-Britt, Fadl, Helena, Wesström, Jan, Lindgren, Peter, Hagberg, Henrik, Jacobsson, Bo, Valentin, Lil, Kuusela, Pihla, Wennerholm, Ulla-Britt, Fadl, Helena, Wesström, Jan, Lindgren, Peter, Hagberg, Henrik, Jacobsson, Bo, and Valentin, Lil

Abstract

Introduction: Universal screening for preterm delivery by adding transvaginal ultrasound measurement of cervical length to routine second trimester ultrasound has been proposed. The aim is to estimate inter- and intraobserver agreement and reliability of second trimester transvaginal ultrasound measurements of cervical length performed by specially trained midwife sonographers. Material and methods: This is a prospective reliability and agreement study performed in seven Swedish ultrasound centers. In total, 18 midwife sonographers specially trained to perform ultrasound measurements of cervical length and 286 women in the second trimester were included. In each center, two midwife sonographers measured cervical length a few minutes apart in the same woman, the number of women examined per examiner pair varying between 24 and 30 (LIVE study). Sixteen midwife sonographers measured cervical length twice >= 2 months apart on 93 video clips (CLIPS study). The main outcome measures were mean difference, limits of agreement, intraclass correlation coefficient, intra-individual standard deviation, repeatability, Cohen's kappa and Fleiss kappa. Results: The limits of agreement and intraclass correlation coefficient of the best examiner pair in the LIVE study were -4.06 to 4.72 mm and 0.91, and those of the poorest were -11.11 to 11.39 mm and 0.31. In the CLIPS study, median (range) intra-individual standard deviation was 2.14 mm (1.40-3.46), repeatability 5.93 mm (3.88-9.58), intraclass correlation coefficient 0.84 (0.66-0.94). Median (range) interobserver agreement for cervical length <= 25 mm in the CLIPS study was 94.6% (84.9%-98.9%) and Cohen's kappa 0.56 (0.12-0.92), median (range) intraobserver agreement was 95.2% (87.1%-98.9%) and Cohen's kappa 0.68 (0.27-0.93). Conclusions: Agreement and reliability of cervical length measurements differed substantially between examiner pairs and examiners. If cervical length measurements are used to guide management there is

Published
2020
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241. Days absent from work due to complications associated with type 2 diabetes : Evidence from 20 years of linked national registry data in Sweden

Author

Persson, Sofie, Johansen, Pierre, Andersson, Emelie, Lindgren, Peter, Thielke, Desiree, Thorsted, Brian Larsen, Jendle, Johan, Carlsson, Katarina Steen, Persson, Sofie, Johansen, Pierre, Andersson, Emelie, Lindgren, Peter, Thielke, Desiree, Thorsted, Brian Larsen, Jendle, Johan, and Carlsson, Katarina Steen

Abstract

Aims: To analyse days absent from work related to individual microvascular, macrovascular and other complications of type 2 diabetes (T2D) and to identify key drivers of absence. Materials and methods: National health and socio-economic individual-level data were analysed for the years 1997 to 2016 for people with T2D, and age-, sex- and residential region-matched controls (5:1) using linkage to Swedish national administrative registers, based on personal identity numbers. Regression analyses accounting for individual-level clustering and education were estimated to obtain days absent by individual complications. Alternative analyses, for example, workforce indicator and age subgroups, were explored for robustness and comparison purposes. Results: A total of 413 000 people with T2D aged <66 years, comprising 4.9 million person-years, was included. The crude proportion with any absence was higher among those with T2D compared to controls (47% vs. 26%) in the index year, and the median (IQR) number of days was higher (223 [77;359] vs. 196 [59;352]) if any absence. Regression analyses showed that complications per se were a key driver of days absent: stroke (+102 days); end-stage renal disease (+70 days); severe vision loss (+56 days); and angina pectoris, heart failure, and osteoarthritis (+53 days each). The alternative analyses showed similar levels of days absent and age subgroups differed in expected directions. Conclusions: This study provides evidence of the persisting impact on productivity from complications that supports continued efforts to reduce risk factors in T2D. Future studies on burden of disease and economic evaluations of new therapies and disease management may use this new set of complication-specific estimates to improve understanding of the value of reducing complications.

Published
2020
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245. Restriction fragment length polymorphism evidence for genetic homology within a pathovar of Pseudomonas syringae

Author

Scholz, Brenda K., Jakobek, Judy L., and Lindgren, Peter B.

Subjects
Pseudomonas syringae -- Research, Genetic polymorphisms -- Research, Biological sciences
Abstract

A restriction fragment length polymorphism (RFLP) analysis of 24 Pseudomonas syringae pv. tabaci strains confirms that a high level of genetic similarity may be present in P. syringae strains pathogenic to specific hosts. Strains of p. syringae pathogenic to tobacco contain conserved hrp genes and argF. BR2R, Pt113R and Pt11528R were the three groups of tobacco isolates classified according to RFLP patterns.

Published
1994

247. Towards a new era in fetal medicine in the Nordic countries

Author

Sitras, Vasilis, Brodszki, Jana, Carlsson, Ylva, Ebbing, Cathrine, Eggebø, Torbjørn, Hardardottir, Hildur, Haugen, Guttorm, Heinonen, Seppo, Iwarsson, Erik, Jacobsson, Bo, Jørgensen, Finn Stener, Lindgren, Peter, Lingman, Göran, Makikallio, Kaarin, Petersen, Olav, Stefanovic, Vedran, Sundberg, Karin Milner, Tabor, Ann, Tekay, Aydin, Tiblad, Eleonor, Vogel, Ida, and Zingenberg, Helle

Subjects
medicine.medical_specialty, Pediatrics, International Cooperation, Psychological intervention, Disease, Scandinavian and Nordic Countries, Subspecialty, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, Intervention (counseling), Health care, medicine, Humans, Molecular diagnostic techniques, 030212 general & internal medicine, Fetal Therapies, high risk pregnancy, 030219 obstetrics & reproductive medicine, ultrasound, business.industry, Obstetrics and Gynecology, Fetal medicine, General Medicine, Economic support, Obstetrics, Fetal Diseases, prenatal screening, Family medicine, embryonic structures, population characteristics, Female, business
Abstract

Fetal medicine is a subspecialty of obstetrics investigating the development, growth and disease of the human fetus. The advances in fetal imaging (ultrasonography, MRI) and molecular diagnostic techniques, together with the possibility of intervention in utero, make fetal medicine an important, rapidly developing field within women's healthcare. Therefore, a variety of specialists, such as neonatologists, pediatric cardiologists, medical geneticists, radiologists and pediatric surgeons, are necessary to adjunct in the diagnosis and treatment of the fetus as a patient. In this commentary, we provide a description of some organizational and educational aspects of fetal medicine in the Nordic countries, using examples of the management of specific conditions such as aneuploidy screening, red cell allo-immunization and fetal interventions. Clearly, there are several cultural, legal, organizational and practical differences between the Nordic countries; these are not necessarily negative, given the high standards of care in all Nordic countries. The scope of the newly founded Nordic Network of Fetal Medicine is to enhance cooperation in clinical practice, education and research between the participant countries. Hopefully, this initiative will find the necessary political and economic support from the national authorities and bring a new era in the field of fetal medicine in the Nordic region.

Published
2016
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249. "Green Multi Business Models" How to Measure Green Business Models and Green Business Model Innovation?

Author

Lindgren, Peter, Knoth, Niklas Stoyan Hornbæk, Sureshkumar, Sukanthan, Friedrich, Mathilde Fogh, and Adomaityte, Rita

Subjects
GREEN business, GREEN technology, BUSINESS models, INNOVATIONS in business, BUSINESS literature, BUSINESS development
Abstract

Ever since the branching of the sustainable and circular literature on business models of the late 2000s and early 2010´s, academia´s, businesses and societies have been experimenting with how to measure green business models. Green Business Model design—creating, capturing, delivering, receiving and consuming TO BE Business Models, Business Model Reconfiguration—focusing on changing AS IS Business Models into becoming or being green and Green Business Model Development—focusing on the tactical parameters of Green Business Models are 3 very different areas of measuring green related to business models and business model innovation. Several tools and actions can in these cases be taken into consideration, when measuring Green Business Models and Green Business Model Innovation. However, it seems as if there is a gap in literature and practice on how to really measure these Green BM Parameters. More specifically—How to measure green related to business models and How to measure green related to business model innovation. None seems yet to be able to measure green business models in real time and none seems to offer green business model measurement on all Green Business Model Parameters in symbiosis with monetary business model parameters. One of the reasons is that there is no clear definitions of green business model parameters although numerous green certificates exist, and several consultancies capitalise heavily on the billion dollar green business model certificate ecosystem for measuring and validating transformation of "AS IS" and "TO BE" business model ecosystems, businesses and their related business models into green. Most definitions and certificates also seem to be pure static and adapted as copies of former iso measurement standards. Very few offer and use advanced technologies to measure the green business model parameters in real-time. Further there is a lack of advanced measurement technologies that are able to measure on all green business model parameters within internet time together with monetary business model parameters. The paper presents some preliminary work on green business model measuring based on data from 240 SME businesses and reports on some preliminary work on a Green Business Model Dashboard in the EU Interreg, Kask GREENBIZZ project aimed at measuring—How green a business and its related business models really are?—and in real time. [ABSTRACT FROM AUTHOR]

Published
2021
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250. Context-Aware Holographic Communication Based on Semantic Knowledge Extraction.

Author

Manolova, Agata, Tonchev, Krasimir, Poulkov, Vladimir, Dixir, Sudhir, and Lindgren, Peter

Subjects
BEHAVIORAL assessment, TELECOMMUNICATION, INNOVATIONS in business, RESOURCE allocation
Abstract

Augmented, mixed and virtual reality are changing the way people interact and communicate. Five dimensional communications and services, integrating information from all human senses are expected to emerge, together with holographic communications (HC), providing a truly immersive experience. HC presents a lot of challenges in terms of data gathering and transmission, demanding Artificial Intelligence empowered communication technologies such as 5G. The goal of the paper is to present a model of a context-aware holographic architecture for real time communication based on semantic knowledge extraction. This architecture will require analyzing, combining and developing methods and algorithms for: 3D human body model acquisition; semantic knowledge extraction with deep neural networks to predict human behaviour; analysis of biometric modalities; context-aware optimization of network resource allocation for the purpose of creating a multi-party, from-capturing-to-rendering HC framework. We illustrate its practical deployment in a scenario that can open new opportunities in user experience and business model innovation. [ABSTRACT FROM AUTHOR]

Published
2021
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