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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity
- Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Kai Ringwald, Julia-Katharina Pfarr, Clemens Bordin, Nina Peusch, Olaf Steinsträter, Dominik Grotegerd, Katharina Dohm, Susanne Meinert, Katharina Förster, Ronny Redlich, Nils Opel, Tim Hahn, Andreas Jansen, Andreas J. Forstner, Fabian Streit, Stephanie H. Witt, Marcella Rietschel, Bertram Müller-Myhsok, Markus M. Nöthen, Udo Dannlowski, Axel Krug, Tilo Kircher, Igor Nenadić
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- Journal:
- Psychological Medicine / Volume 52 / Issue 16 / December 2022
- Published online by Cambridge University Press:
- 08 April 2021, pp. 4127-4138
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Background
MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
MethodsWe extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
ResultsThe PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
ConclusionsChanges in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
An ultra-wide bandwidth (704 to 4 032 MHz) receiver for the Parkes radio telescope
- George Hobbs, Richard N. Manchester, Alex Dunning, Andrew Jameson, Paul Roberts, Daniel George, J. A. Green, John Tuthill, Lawrence Toomey, Jane F. Kaczmarek, Stacy Mader, Malte Marquarding, Azeem Ahmed, Shaun W. Amy, Matthew Bailes, Ron Beresford, N. D. R. Bhat, Douglas C.-J. Bock, Michael Bourne, Mark Bowen, Michael Brothers, Andrew D. Cameron, Ettore Carretti, Nick Carter, Santy Castillo, Raji Chekkala, Wan Cheng, Yoon Chung, Daniel A. Craig, Shi Dai, Joanne Dawson, James Dempsey, Paul Doherty, Bin Dong, Philip Edwards, Tuohutinuer Ergesh, Xuyang Gao, JinLin Han, Douglas Hayman, Balthasar Indermuehle, Kanapathippillai Jeganathan, Simon Johnston, Henry Kanoniuk, Michael Kesteven, Michael Kramer, Mark Leach, Vince Mcintyre, Vanessa Moss, Stefan Osłowski, Chris Phillips, Nathan Pope, Brett Preisig, Daniel Price, Ken Reeves, Les Reilly, John Reynolds, Tim Robishaw, Peter Roush, Tim Ruckley, Elaine Sadler, John Sarkissian, Sean Severs, Ryan Shannon, Ken Smart, Malcolm Smith, Stephanie Smith, Charlotte Sobey, Lister Staveley-Smith, Anastasios Tzioumis, Willem van Straten, Nina Wang, Linqing Wen, Matthew Whiting
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 08 April 2020, e012
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We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band ( ${\sim}60\%$ ), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Healthy women with severe early life trauma show altered neural facilitation of emotion inhibition under acute stress
- Sabrina Golde, Katja Wingenfeld, Antje Riepenhausen, Nina Schröter, Juliane Fleischer, Jens Prüssner, Simone Grimm, Yan Fan, Julian Hellmann-Regen, Anne Beck, Stefan M. Gold, Christian Otte
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- Journal:
- Psychological Medicine / Volume 50 / Issue 12 / September 2020
- Published online by Cambridge University Press:
- 29 August 2019, pp. 2075-2084
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Background
Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood.
MethodsThe present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women.
ResultsUnder stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain–behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation.
ConclusionNeural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.
Molecular mechanisms of xeroderma pigmentosum (XP) proteins
- Sandra C. Koch, Nina Simon, Charlotte Ebert, Thomas Carell
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- Journal:
- Quarterly Reviews of Biophysics / Volume 49 / 2016
- Published online by Cambridge University Press:
- 10 February 2016, e5
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Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA–XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase ɳ, which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins.
Global trends and patterns in material use
- Fridolin Krausmann, Anke Schaffartzik, Andreas Mayer, Simone Gingrich, Nina Eisenmenger
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1545 / 2013
- Published online by Cambridge University Press:
- 30 September 2013, mrss13-1545-k04-03
- Print publication:
- 2013
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Humanity currently extracts almost 70 billion tons of materials per year. During the last century global materials extraction and use have increased by one order of magnitude. Growth accelerated in the last decade, when materials extraction grew with the global economy at an annual rate of 3.6%. For sustainable development it is of key importance to understand the spatial and temporal dynamics of global material use and the underlying drivers. This paper explores changes in global material use during the last century from a systemic perspective based on the concept of socio-economic metabolism.
In recent years socio-economic (or, more narrowly termed industrial) metabolism became a prominent concept in sustainability science as many global sustainability problems are directly associated with humanities growing demand for raw materials and their transformation into wastes and emissions after processing and use. Material Flow Analysis (MFA) is one of the approaches available to study social metabolism. It provides data and headline indicators for resource use in national economies and is widely used in science and by policy makers.
This paper presents results from a global material flow analysis and explores long term the development of global material extraction and use. It shows that in particular the period after WWII was characterized by a rapid expansion of resource use, driven by both population and economic growth. Within this period a shift from the dominance of renewable biomass towards mineral and fossil materials, which now account for 70% of all used materials, was observed. Overall, material use increased at a slower pace than the global economy, but faster than world population. As a consequence, material intensity (i.e. the amount of materials required per unit of GDP) declined throughout the 20th century, while materials use per capita doubled. The use of materials is by no means equally distributed around the globe. Per capita material use varies by a factor of 20 across countries. At the turn of the millennium, 15% of the global population living in industrialized countries were using half of all mineral and fossil resources; in contrast, the least developed countries, inhabiting 11% of global population, appropriated only 1% of these strategically important materials. In recent years, however, the emerging economies gained significance as drivers for physical growth. So far there is no evidence that growth of global materials use is slowing down. The paper discusses the implications of the results from the material flow analysis for sustainable development.
Highly controlled crystallite size and crystallinity of pure and iron-doped anatase-TiO2 nanocrystals by continuous flow supercritical synthesis
- Jian-Li Mi, Simon Johnsen, Casper Clausen, Peter Hald, Nina Lock, Lasse Sø, Bo B. Iversen
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- Journal:
- Journal of Materials Research / Volume 28 / Issue 3 / 14 February 2013
- Published online by Cambridge University Press:
- 30 July 2012, pp. 333-339
- Print publication:
- 14 February 2013
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High purity anatase titanium dioxide (TiO2) and iron (Fe)-doped TiO2 nanocrystals were prepared by a continuous flow synthesis method using isopropanol-water mixtures as solvent in supercritical or near-critical conditions. The method allows complete control of size (5–20 nm) and crystallinity (10–100%) of the nanoparticles and provides quick synthesis with a residence time of ∼10 s that can be scaled up to commercial production. It is found that the average crystallite size can be easily controlled by adjusting the ratio between isopropanol and water in the solvent, whereas the crystallinity is mainly controlled by the reaction temperature. As-prepared Fe-doped TiO2 nanoparticles appear to be single phase, but Fe3+ ions most likely do not occupy the Ti4+ sites in the anatase TiO2 crystal structure.
Strain Analysis of Copper Films During Wet-Chemical Deposition.
- Ralf Brüning, Laura K. Perry, Bruce Muir, Alaaedeen Abuzir, Simon Bamberg, Wolfgang Friz, Nina Dambrowsky, Frank Brüning
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1400 / 2012
- Published online by Cambridge University Press:
- 17 January 2012, mrsf11-1400-s05-05
- Print publication:
- 2012
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Electroless (chemical) copper deposition, followed by electrolytic (galvanic) copper deposition, is used to construct electrical interconnects for electronic components on insulating substrate materials. As smooth substrates, such as glass or flexible materials like polyimide or polyethylene terephthalate, are used increasingly, achieving the required level of adhesion becomes more difficult. The film strain is one key variable that influences film adhesion. Standard X-ray diffraction based strain analysis was adapted for in situ strain monitoring during and after wet-chemical copper deposition. The results show that adding nickel suppresses an initial compressive strain that frequently appears in Ni-free baths. Adding ruthenium complexes to a standardized electroless copper formulation gradually shifts the strain from tensile to compressive. Spontaneous recrystallization at room temperature was monitored in detail for films obtained by direct current galvanic copper plating.
4 - Fig–fig wasp mutualism: the fall of the strict cospeciation paradigm?
- Edited by Sébastien Patiny, Université de Mons-Hainaut, Belgium
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- Book:
- Evolution of Plant-Pollinator Relationships
- Published online:
- 05 January 2012
- Print publication:
- 08 December 2011, pp 68-102
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Summary
Introduction
At least three classic systems of nursery pollination mutualism are known: the fig (Ficus, Moraceae) – agaonid (Hymenoptera, Chalcidoidea) association (Cook and Rasplus 2003), the yucca (Yucca, Hesperoyucca; Agavaceae) – yucca moths (Tegeticula, Parategeticula; Lepidoptera, Prodoxidae) association (Pellmyr 2003) and the Glodichion (Phyllanthaceae) – Epicephala moths (Lepidoptera, Gracillariidae) association (Kato et al. 2003). All these mutualisms are obligate, which means that each partner depends on the other for its own reproductive success. The insect pollinates the flowers and oviposits in the plant ovaries where the insect larvae subsequently feed on a subset of the developing seeds. A shift from mutualism to parasitism by the pollinating insect would lead to reproduction failure of the plant and, without host shift, to the extinction of both lineages. Therefore, the speciation of mutualistic pollinators is generally believed to be driven by the speciation of their host-plants. In this hypothesis, when an ancestral plant species splits into two daughter species, its mutualistic pollinator also splits. This scenario should result in perfect congruence of hosts and pollinator phylogenies (Farenholz’s rule) (Farenholz 1913). However, this seems increasingly unlikely. Indeed, more and more studies on different coevolved associations show that a strict Farenholz’s rule is not respected, even when a high level of host specificity exists (e.g. Paterson and Banks 2001; Desdevises et al. 2002; Charleston and Perkins 2006).
Topological incongruence between host and associate phylogenetic trees can result from processes like host switching, sorting events (extinction and lineage sorting), duplication events (speciation of the parasite independent of the host), and failure of the associate to diverge when the host diverges (“missing the boat”) (Page 1991; Page 1994; Page and Charleston 1998; Legendre et al. 2002; Charleston and Perkins 2006).
Contributors
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- By Graeme J.M. Alexander, Heung Bae Kim, Michael Burch, Andrew J. Butler, Tanveer Butt, Roy Calne, Edward Cantu, Robert B. Colvin, Paul Corris, Charles Crawley, Hiroshi Date, Francis L. Delmonico, Bimalangshu R. Dey, Kate Drummond, John Dunning, John D. Firth, John Forsythe, Simon M. Gabe, Robert S. Gaston, William Gelson, Paul Gibbs, Alex Gimson, Leo C. Ginns, Samuel Goldfarb, Ryoichi Goto, Walter K. Graham, Simon J.F. Harper, Koji Hashimoto, David G. Healy, Hassan N. Ibrahim, David Ip, Fadi G. Issa, Neville V. Jamieson, David P. Jenkins, Dixon B. Kaufman, Kiran K. Khush, Heung Bae Kim, Andrew A. Klein, John Klinck, Camille Nelson Kotton, Vineeta Kumar, Yael B. Kushner, D. Frank. P. Larkin, Clive J. Lewis, Yvonne H. Luo, Richard S. Luskin, Ernest I. Mandel, James F. Markmann, Lorna Marson, Arthur J. Matas, Mandeep R. Mehra, Stephen J. Middleton, Giorgina Mieli-Vergani, Charles Miller, Sharon Mulroy, Faruk Özalp, Can Ozturk, Jayan Parameshwar, J.S. Parmar, Hari K. Parthasarathy, Nick Pritchard, Cristiano Quintini, Axel O. Rahmel, Chris J. Rudge, Stephan V.B. Schueler, Maria Siemionow, Jacob Simmonds, Peter Slinger, Thomas R. Spitzer, Stuart C. Sweet, Nina E. Tolkoff-Rubin, Steven S.L. Tsui, Khashayar Vakili, R.V. Venkateswaran, Hector Vilca-Melendez, Vladimir Vinarsky, Kathryn J. Wood, Heidi Yeh, David W. Zaas, Jonathan G. Zaroff
- Edited by Andrew A. Klein, Clive J. Lewis, Joren C. Madsen
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- Book:
- Organ Transplantation
- Published online:
- 07 September 2011
- Print publication:
- 11 August 2011, pp vii-x
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