Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes ($\textit{ITGA4 }$ and $\textit{ITGB8}$) and at previously implicated loci ($\textit{ITGAL }$and $\textit{ICAM1}$). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, $\textit{PLCG2}$, and a negative regulator of inflammation, $\textit{SLAMF8}$. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.This work was co-funded by the Wellcome Trust [098051] and the Medical Research Council, UK [MR/J00314X/1]. Case collections were supported by Crohn’s and Colitis UK. KMdL, LM, CAL, YL, DR, JG-A, NJP, CAA and JCB are supported by the Wellcome Trust [098051; 093885/Z/10/Z; 094491/Z/10/Z]. KMdL is supported by a Woolf Fisher Trust scholarship. CAL is a clinical lecturer funded by the NIHR. We thank Anna Stanton for co-ordinating the Guy’s and St Thomas’ patient recruitment. We acknowledge support from the Department of Health via the NIHR comprehensive Biomedical Research Centre awards to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and to Addenbrooke’s Hospital, Cambridge in partnership with the University of Cambridge. This research was also supported by the NIHR Newcastle Biomedical Research Centre. The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council

Engineers, Social Scientists, and Nuclear Power

The PAGES collaboration (University of Tokyo and University of California, Berkeley) brought together nuclear engineers and social scientists to try out new ways of engaging engineering graduate students with societal issues around nuclear power. The program was built around seminars and summer schools. Because of the Fukushima Daiichi disaster, it ended up culminating in a weeklong program for students in summer 2011 to examine the Fukushima Daiichi accident as a socio-technical catastrophe and an invitation to rethink nuclear engineers’ possible roles in a post-Fukushima world. This chapter reflects on the PAGES collaboration and the Fukushima Daiichi summer school from the perspective of one of the social scientists involved. It narrates the experience of collaborating across disciplinary boundaries at a moment of challenge and in a space where social science is not well anchored to start. Out of this narrative, the chapter aims to draw some potentially generalizable suggestions for social scientists who are trying to engage engineers and graduate students, given the constraints of time, attention, and trust

Heisenberg in the atomic age: science and the public sphere

The end of the Second World War opened a new era for science in public life. Heisenberg in the Atomic Age explores the transformations of science's public presence in the postwar Federal Republic of Germany. It shows how Heisenberg's philosophical commentaries, circulating in the mass media, secured his role as science's public philosopher, and it reflects on his policy engagements and public political stands, which helped redefine the relationship between science and the state. With deep archival grounding, the book tracks Heisenberg's interactions with intellectuals from Heidegger to Habermas and political leaders from Adenauer to Brandt. It also traces his evolving statements about his wartime research on nuclear fission for the National Socialist regime. Working between the history of science and German history, the book's central theme is the place of scientific rationality in public life - after the atomic bomb, in the wake of the Third Reich

Conference "The Cultural Alchemy of the Exact Sciences : Revisiting the Forman Thesis"

This volume reprints Paul Forman's classic papers on the history of physics in post-World War I Germany and the invention of quantum mechanics. The Forman thesis has become famous as the first argument in favor of the cultural conditioning of scientific knowledge, in particular for its demonstration of the historical connection between the culture of Weimar Germany - known for its irrationality and antiscientism - and the emerging concept of quantum acausality.This volume reprints Paul Forman's classic papers on the history of physics in post-World War I Germany and the invention of quantum mechanics. The Forman thesis has become famous as the first argument in favor of the cultural conditioning of scientific knowledge, in particular for its demonstration of the historical connection between the culture of Weimar Germany - known for its irrationality and antiscientism - and the emerging concept of quantum acausality. At the 2007 international conference in Vancouver, Canada, leading historians of physics discussed the implications of the Forman thesis in the historiography of modern science. Their papers collected in this volume represent a cutting-edge research on the history of quantum revolution

Reflections on the Fukushima Daiichi nuclear accident: toward social-scientific literacy and engineering resilience

This book focuses on nuclear engineering education in the post-Fukushima era. It was edited by the organizers of the summer school held in August 2011 in University of California, Berkeley, as part of a collaborative program between the University of Tokyo and UC Berkeley. Motivated by the particular relevance and importance of social-scientific approaches to various crucial aspects of nuclear technology, special emphasis was placed on integrating nuclear science and engineering with social science. The book consists of the lectures given in 2011 summer school and additional chapters that cover developments in the past three years since the accident. It provides an arena for discussions to find and create a renewed platform for engineering practices, and thus nuclear engineering education, which are essential in the post-Fukushima era for nurturing nuclear engineers who need to be both technically competent and trusted in society

Erratum to: Integrating Social-Scientific Literacy in Nuclear Engineering Education

This introductory chapter explains the historical background, outline, basic concept, and objective of the Program for Advanced Graduate Education system for nuclear science and engineering with Social scientific literacy (PAGES), under which the 2011 summer school was organized and this book was developed. Early efforts and trials in PAGES started in 2008 toward integrating social sciences in nuclear engineering education mainly by organizing summer schools as a test bed. Various important insights on how pedagogically effective integration could and should be achieved were obtained through the summer schools held in 2008–2010. When the Fukushima Daiichi accident occurred in March 2011, the organizing committee of the 2011 summer school, which consisted of the authors of this chapter, immediately recognized that this would be a time when PAGES faced a test with regard to its effectiveness, and the previous efforts under PAGES should be fully utilized to understand and address the accident. The organizing committee concluded that while it is still in its infancy, the PAGES approach successfully established an integrated framework for both engineers and social scientists. It changed the perspectives of the participants, both the students and the organizers, and it laid groundwork that the organizers hope that they and others will be able to build upon