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Investigating Transcranial Direct Current Stimulation (TDCS) in obsessive compulsive disorder (OCD): a double-blind, sham-controlled, cross-over randomised trial
- Eduardo Cinosi, David Baldwin, Tim Gale, Matt Garner, Natalie Hall, Daniel Meron, Nick Sireau, David Wellsted, Solange Wyatt, Naomi A Fineberg
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, pp. S14-S15
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Aims
Obsessive Compulsive Disorder is a disabling and difficult-to-treat condition, new treatment options are needed to improve health outcomes. Transcranial Direct Current Stimulation, a non-invasive form of neurostimulation, has shown positive results in a small number of studies as a safe and potentially efficacious treatment for OCD. There nevertheless remains uncertainty about the optimal stimulation protocol, magnitude and duration of effect, acceptability, tolerability and practicality of applying tDCS clinical settings. As existing data are inadequate to support a full-scale trial, we will deliver a feasibility study to address key research questions and knowledge gaps to enable the design and the development of the most efficient, cost effective, definitive trial.
MethodWe designed Feasibility And Acceptability Of Transcranial Stimulation In Obsessive Compulsive Symptoms (FEATSOCS), a double-blind, sham-controlled, cross-over randomised multicentre study in 25 adults with OCD. We will stimulate the two most promising cortical sites, the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated, given in counterbalanced order. Each course comprises four 20 minutes-stimulations, delivered over two consecutive days, separated by at least four weeks’ washout period. Blinded raters will regularly assess clinical outcomes before, during and up to four weeks after stimulation using validated scales. We will include relevant neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning.
ResultFEATSOCS trial is currently underway and recruiting. Owing to the impact of COVID-19, a recruitment extension has been granted. At the study end, we will analyse the feasibility outcomes, magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure to estimate effect size, and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, the impact on their overall quality of life and their views on the potential of tDCS as home based-intervention.
ConclusionFurther evidence is needed to establish whether tDCS could join the treatment armamentarium of OCD. The clinical outcomes in FEATSOCS will enable to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the tDCS in OCD in a full scale trial.
The funder for this study is the National Institute for Health Research Programme, Research for Patient Benefit (RfPB) [Ref. no PB-PG-1216-20005]. Extra funding to allow study extension was provided by Orchard OCD. This study has received full ethics committee approval and protocol amendments approval form the Cambridge and Hertfordshire NHS Research Ethics Committee, IRAS Project ID 254507, REC ref: 19/EE/0046.
Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. 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Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. 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Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- Book:
- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
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- 20 September 2010, pp xi-xliv
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6 - Hagfish: A Model for Early Endothelium
- from PART I - CONTEXT
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- By Pavan K. Cheruvu, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, Daniel Gale, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, Ann M. Dvorak, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, David Haig, Harvard University, Cambridge, Massachusetts, William C. Aird, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Mount Desert Island Biological Laboratory, Salisbury Cove, Maine
- Edited by William C. Aird, Harvard University, Massachusetts
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- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 66-73
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Summary
Evolution can be viewed as a gradual accumulation of adaptive mutations against a background of neutral change. Intraspecific diversity may be the substrate of evolution, but intraorganismal diversity – the emergence of new proteins, new cell types, and new tissue functionalities – is its exquisite product. Each organism, indeed each organ, is a complex, interlocking “bundle of adaptations.” The endothelium is no exception. Over the last three decades, the notion that the endothelium represents an uncomplicated permeability-selective barrier between blood and interstitium has been revised considerably. Endothelial cells (ECs) are now known to regulate inflammation, hemostasis, vasomotor tone, growth and proliferation of other cells, antigen presentation, extravasation of immune cells, and metabolism of tissue- or blood-derived hormones. These functions are differentially regulated in space and time (reviewed in 1). Endothelial cell heterogeneity reflects the capacity of the endothelium to adapt and respond to the unique demands of the underlying tissue (reviewed in 2). An important goal is to dissect the complex molecular mechanisms underlying endothelial cell function and dysfunction.
THE CALL FOR AN EVOLUTIONARY APPROACH
Why study comparative and evolutionary vascular biology? First, evolution is at heart an historical science, and curiosity drives us to understand the narrative of biological change as well as patterns that may underlie this change. Second, the study of simple models has for centuries been an indispensable tool for sharpening our analysis of more complex biological systems. One is reminded of the contributions of Mendel on Pisum sativum, Morgan on Drosophila melanogaster, and Kandel on Aplysia californica.
Enhanced Emission from a Light-Emitting Diode Modified by a Photonic Crystal
- Alexei A. Erchak, Daniel J. Ripin, Shanhui Fan, John D. Joannopoulos, Erich P. Ippen, Gale S. Petrich, Leslie A. Kolodziejski
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- MRS Online Proceedings Library Archive / Volume 637 / 2000
- Published online by Cambridge University Press:
- 15 March 2011, E2.8
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- 2000
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Enhanced light output is observed from a light-emitting diode (LED) structure containing a two-dimensional (2D) photonic crystal. The capture of emitted light into planar waveguide modes reduces the extraction efficiency of LEDs. Here, 2D photonic crystals are utilized to: 1) enhance the extraction of light in the vertical direction from an LED and 2) enhance optical pumping by directly coupling light from a pump laser into the LED structure. Spatially and spectrally-resolved photoluminescence (PL) is used to characterize the enhancements. A 100-fold enhancement in extraction for a single wavelength into the vertical direction is obtained without the photonic crystal penetrating the active material.
Electrical and Optical Interconnection-Technology based on Ormocer® - Inorganic-Organic Hybrid Materials
- Michael Popall, Ralf Buestrich, Frank Kahlenberg, Annika Andersson, Joacim Haglund, Mats E. Robertsson, Gerd Blau, Mike Gale, Oliver Rösch, Alexander Dabek, Jens Neumann-Rodekirch, Lubomir Cergel, Daniel Lambert
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- Journal:
- MRS Online Proceedings Library Archive / Volume 628 / 2000
- Published online by Cambridge University Press:
- 01 February 2011, CC9.4
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- 2000
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Photopatternable hybrid inorganic-organic polymers with negative resist behaviour have been developed and tested for evaluation in optical and electrical interconnection technology. They are composed of inorganic oxidic structures cross-linked or substituted by organic groups. The synthesis starts from organosilane precursors reacted by sol-gel-processing in combination with organic crosslinking of polymerisable organic functions. As a result of these functionalities the properties of the ORMOCER®s are adjusted to the particular applications. Systematic variation of composition combined with adaptation to micro system technology allows great flexibility in processing. The main features of these materials are:
• Combined use as dielectric and passivation layers in electrical systems and devices as well as core and cladding for optical applications enables e/o applications with high integration levels.
• Postbaking at moderate temperatures (120 - 170 °C) enables processing on low-cost substrates such as FR-4 (a glass-fibre reinforced epoxy-polymer).
• Easily adaptable to thin film technology: spin-on with planarisation > 90 %, via diameters down to 20 μm and high aspect ratio for optical waveguides have been achieved.
Synthesis, modification of the resins towards technological needs, their thin film technology and the resulting demonstrators will be discussed.
