Suchergebnisse

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10−8) or suggestively genome wide (p < 2.3 × 10−6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass. ; We acknowledge the essential role of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium in development and support of this manuscript. CHARGE members include the Netherland's Rotterdam Study (RS), Framingham Heart Study (FHS), Cardiovascular Health Study (CHS), the NHLBI's Atherosclerosis Risk in Communities (ARIC) Study, and Iceland's Age, Gene/Environment Susceptibility (AGES) Reykjavik Study. Age, Gene/Environment Susceptibility Reykjavik Study (AGES-Reykjavik): has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, (VSN: 00-063) and the Data Protection Authority. The researchers are indebted to the participants for their willingness to participate in the study. Old Order Amish (OOA): this work was supported by NIH research grants U01 HL72515, U01 GM074518, R01 HL088119, R01 AR046838, and U01 HL084756. Partial funding was also provided by the Mid-Atlantic Nutrition and Obesity Research Center of Maryland (P30 DK072488).). L.M.Y.-A. was supported by F32AR059469 from NIH/NIAMS. M.F. was supported by American Heart Association grant 10SDG2690004. Cardiovascular Health Study (CHS): This CHS research was supported by NHLBI contracts N01-HC- 85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-85239, and by HHSN268201200036C and NHLBI grants HL080295, HL087652, HL105756, HL103612, HL120393, and HL130114 with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at Cedars-Sinai Medical Center was supported in part by the National Center for Research Resources, grant UL1RR033176, and is now at the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124; in addition to the National Institute of Diabetes and Digestive and Kidney Disease grant DK063491 to the Southern California Diabetes Endocrinology Research Center. CoLaus: The CoLaus study received financial contributions from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, and 33CS30-148401). We thank Vincent Mooser and Gérard Waeber, Co-PIs of the CoLaus study. Special thanks to Yolande Barreau, Mathieu Firmann, Vladimir Mayor, Anne-Lise Bastian, Binasa Ramic, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne Ecoffey, and Sylvie Mermoud for data collection. Data analysis was supervised by Sven Bergmann and Jacques S. Beckmann. The computations for this paper were performed in part at the Vital-IT Center for high-performance computing of the Swiss Institute of Bioinformatics. deCODE Study: The study was funded by deCODE Genetics, ehf. We thank all the participants of this study, the staff of deCODE Genetics core facilities and recruitment center and the densitometry clinic at the University Hospital for their important contributions to this work. The EPIC Study: The EPIC Obesity study is funded by Cancer Research United Kingdom and the Medical Research Council. I.B. acknowledges support from EU FP6 funding (contract no. LSHM-CT-2003-503041) and by the Wellcome Trust (WT098051). Erasmus Rucphen Family (ERF) Study: The study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Centre for Medical Systems Biology (CMSB), and the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413. We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and Peter Snijders for his help in data collection. Fenland: The Fenland Study is funded by the Wellcome Trust and the Medical Research Council, as well as by the Support for Science Funding programme and CamStrad. We are grateful to all the volunteers for their time and help, and to the General Practitioners and practice staff for help with recruitment. We thank the Fenland Study co-ordination team and the Field Epidemiology team of the MRC Epidemiology Unit for recruitment and clinical testing. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF—1333-00124 and Sapere Aude program grant DFF—1331-00730B). Framingham Osteoporosis Study (FOS)/Framingham Heart Study (FHS): The study was funded by grants from the US National Institute for Arthritis, Musculoskeletal and Skin Diseases and National Institute on Aging (R01 AR 41398 and U24AG051129; D.P.K. and R01AR057118; D.K. D.K. was also supported by FP7-PEOPLE-2012-Marie Curie Career Integration Grants (CIG)). The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine were supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (N02-HL-6-4278). Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. eQTL HOb Study: The study was supported by Genome Quebec, Genome Canada and the Canadian Institutes of Health Research (CIHR). Gothenburg Osteoporosis and Obesity Determinants Study (GOOD): The study was funded by the Swedish Research Council, the Swedish Foundation for Strategic Research, The ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Emil and Vera Cornell Foundation, the Torsten and Ragnar Söderberg's Foundation, Petrus and Augusta Hedlunds Foundation, the Västra Götaland Foundation, and the Göteborg Medical Society. We would like to thank Dr Tobias A. Knoch, Luc V. de Zeeuw, Anis Abuseiris, and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and # 01 IG 07015G for access to their grid resources. We also thank Karol Estrada, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands for advice regarding the grid resources. Health Aging and Body Composition Study (Health ABC): This study was funded by the National Institutes of Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. Indiana: We thank the individuals who participated in this study, as well as the study coordinators, without whom this work would not have been possible. This work was supported by National Institutes of Health grants R01 AG 041517 and M01 RR-00750. Genotyping services were provided by CIDR. CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. Kora (KORA F3 and KORA F4): The KORA research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. The London Life Sciences Population (LOLIPOP): The study was funded by the British Heart Foundation, Wellcome Trust, the Medical Research Council, and Kidney Research UK. The study also receives support from a National Institute for Health Research (NIHR) programme grant. Rotterdam Study (RSI, RSII & RSIII): The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organisation of Scientific Research NWO Investments (no. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project no. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, PhD, for the creation and analysis of imputed data. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. We thank Dr Karol Estrada, Dr Fernando Rivadeneira, Dr Tobias A. Knoch, Anis Abuseiris, and Rob de Graaf (Erasmus MC Rotterdam, The Netherlands) for their help in creating GRIMP, and we thank BigGRID, MediGRID, and Services@MediGRID/D-Grid (funded by the German Bundesministerium fuer Forschung und Technology; grants 01 AK 803 A-H, 01 IG 07015G) for access to their grid computing resources. Rush Memory and Aging Project (MAP): The Memory and Aging Project was supported by National Institute on Aging grants R01AG17917, R01AG15819, and R01AG24480, the Illinois Department of Public Health, the Rush Clinical Translational Science Consortium, and a gift from Ms Marsha Dowd. TwinsUK (TUK): The study was funded by the Wellcome Trust, Arthritis Research UK, and the Chronic Disease Research Foundation. The study also received support from a National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. We thank the staff and volunteers of the TwinsUK study. The study was also supported by Israel Science Foundation, grant number 994/10. Age, Gene/Environment Susceptibility Reykjavik Study (AGES-Reykjavik) has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee (VSN: 00-063) and the Data Protection Authority. The researchers are indebted to the participants for their willingness to participate in the study. Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF (grants #16SV5536K, #16SV5537, #16SV5538, and #16SV5837; previously #01UW0808)). Additional contributions (e.g., financial, equipment, logistics, personnel) are made from each of the other participating sites, i.e., the Max Planck Institute for Human Development (MPIB), Max Planck Institute for Molecular Genetics (MPIMG), Charite University Medicine, German Institute for Economic Research (DIW), all located in Berlin, Germany, and University of Lübeck in Lübeck, Germany. B-vitamins in the prevention of osteoporotic fractures (B-PROOF): B-PROOF is supported and funded by The Netherlands Organization for Health Research and Development (ZonMw, grant 6130.0031), the Hague; unrestricted grant from NZO (Dutch Dairy Association), Zoetermeer; Orthica, Almere; NCHA (Netherlands Consortium Healthy Ageing) Leiden/Rotterdam; Ministry of Economic Affairs, Agriculture and Innovation (project KB-15-004-003), the Hague; Wageningen University, Wageningen; VU University Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam. All organizations are based in the Netherlands. We thank Dr Tobias A. Knoch, Anis Abuseiris, Karol Estrada, and Rob de Graaf as well as their institutions the Erasmus Grid Office, Erasmus MC Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology (grants #01 AK 803 A-H and #01 IG 07015G) for access to their gird resources. Further, we gratefully thank all participants. Calcium Intake Fracture Outcome Study (CAIFOS): This study was funded by Healthway Health Promotion Foundation of Western Australia, Australasian Menopause Society and the Australian National Health and Medical Research Council Project Grants (254627, 303169, and 572604). We are grateful to the participants of the CAIFOS Study. The salary of Dr Lewis is supported by a National Health and Medical Research Council of Australia Career Development Fellowship. Danish Osteoporosis Study (DOPS): The study was supported by Karen Elise Jensen foundation. Family Heart Study (FamHS): The study was supported by NIH grants R01-HL-117078, R01-HL-087700, and R01-HL-088215 from NHLBI; and R01-DK-089256 and R01-DK-075681 from NIDDK. GenMets (Health 2000): S.R. was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (213506 and 129680), Academy of Finland (251217), the Finnish foundation for Cardiovascular Research and the Sigrid Juselius Foundation. S.M. was supported by grants #136895 and #141005, V.S. by grants #139635 and 129494, and M.P. by grant #269517 from the Academy of Finland and a grant from the Finnish Foundation for Cardiovascular Research. M.P. was supported by the Yrjö Jahnsson Foundation. Helsinki Birth Cohort Study (HBCS): We thank all study participants as well as everybody involved in the HBCS. HBCS has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Samfundet Folkhälsann, Novo Nordisk Foundation, Liv och Hälsa, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, European Science Foundation (EUROSTRESS), Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation, and Wellcome Trust (grant number WT089062). Johnston County Study: The Johnston County Osteoarthritis Project is supported in part by cooperative agreements S043, S1734, and S3486 from the Centers for Disease Control and Prevention/Association of Schools of Public Health; the NIAMS Multipurpose Arthritis and Musculoskeletal Disease Center grant 5-P60-AR30701; and the NIAMS Multidisciplinary Clinical Research Center grant 5 P60 AR49465-03. Genotyping services were provided by Algynomics company. Korean Genome Epidemiology Study (KoGES): Korean Genome Epidemiology Study (KoGES): This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (found 2001-347-6111-221, 2002-347-6111-221, 2009-E71007-00, 2010-E71004-00). Kora F3 and Kora F4: The KORA research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. LOLIP-REP-IA610: The study was supported by the Wellcome Trust. We thank the participants and research teams involved in LOLIPOP. LOLIP-REP-IA_I: The study was supported by the British Heart Foundation Grant SP/04/002. LOLIP-REP-IA_P: The study was supported by the British Heart Foundation Grant SP/04/002. METSIM: The study was supported by the Academy of Finland, the Finnish Diabetes Research Foundation, the Finnish Cardiovascular Research Foundation, the Strategic Research Funding from the University of Eastern Finland, Kuopio, and the EVO grant 5263 from the Kuopio University Hospital. MrOS Sweden: Financial support was received from the Swedish Research Council (2006-3832), the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Söderberg's Foundation, Petrus and Augusta Hedlunds Foundation, the Västra Götaland Foundation, the Göteborg Medical Society, and the Novo Nordisk foundation. Greta and Johan Kock Foundation, A. Påhlsson Foundation, A. Osterlund Foundation, Malmö University Hospital Research Foundation, Research and Development Council of Region Skåne, Sweden, the Swedish Medical Society. MrOS US: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provided funding for the MrOS ancillary study "GWAS in MrOS and SOF" under the grant number RC2ARO58973. Osteoporosis Prospective Risk Assessment study (OPRA): This work was supported by grants from the Swedish Research Council (K2009-53X-14691-07-3, K2010-77PK-21362-01-2), FAS (grant 2007-2125), Greta and Johan Kock Foundation, A. Påhlsson Foundation, A. Osterlund Foundation, Malmö University Hospital Research Foundation, Research and Development Council of Region Skåne, Sweden, the Swedish Medical Society. We are thankful to all the women who kindly participated in the study and to the staff at the Clinical and Molecular Osteoporosis Research Unit for helping in recruitment of study individuals. Orkney Complex Disease Study (ORCADES): ORCADES was supported by the Chief Scientist Office of the Scottish Government (CZB/4/276, CZB/4/710), the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK (17539) and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We acknowledge the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney. PEAK 25: This work was supported by grants from the Swedish Research Council (K2009-53X-14691-07-3, K2010-77PK-21362-01-2), FAS (grant 2007-2125), Greta and Johan Kock Foundation, A. Påhlsson Foundation, A. Osterlund Foundation, Malmö University Hospital Research Foundation, Research and Development Council of Region Skåne, Sweden, the Swedish Medical Society. We are thankful to all the women who kindly participated in the study and to the staff at the Clinical and Molecular Osteoporosis Research Unit for helping in recruitment of study individuals. Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS): The study was supported by grants from the Swedish research council (projects 2008-2202 and 2005-8214) and ALF/LUA research grants from Uppsala university hospital, Uppsala, Sweden. Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC): The RISC study is supported by European Union Grant QLG1-CT-2001-01252 and AstraZeneca. We thank Merck Research Labs for conducting DNA genotyping on RISC samples.Rotterdam III: Rotterdam Study (RS): See discovery. SHIP and SHIP TREND: This work was supported by SHIP, which is part of the Community Medicine Research Network of the University of Greifswald, Germany, by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania and the network "Greifswald Approach to Individualized Medicine (GANI_MED)" funded by the Federal Ministry of Education and Research (03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the "Center of Knowledge Interchange" program of the Siemens. A.G. and the Cache´ Campus program of the InterSystems GmbH. The SHIP authors are grateful to the contribution of Florian Ernst, Anja Wiechert, and Astrid Petersmann in generating the SNP data and to Mario Stanke for the opportunity to use his Server Cluster for SNP Imputation. Data analyses were further supported by the German Research Foundation (DFG Vo 955/10-1) and the Federal Ministry of Nutrition, Agriculture and Consumer's Safety. SOF: The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provided funding for the SOF ancillary study "GWAS in MrOS and SOF" under the grant number RC2ARO58973. Uppsala Longitudinal Study of Adult Men (ULSAM): The study was funded by grants from the Swedish research council (projects 2008-2202 and 2005-8214), the Wallenberg foundation, and ALF/LUA research grants from Uppsala university hospital, Uppsala, Sweden. Andrew P. Morris is a Wellcome Trust Senior Fellow in Basic Biomedical Science, grant number WT098017. CROATIA-VIS (VIS): The CROATIA-Vis study was funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). We acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland. Women's Health Initiative (WHI): The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100–2, 32105–6, 32108–9, 32111–13, 32115, 32118–32119, 32122, 42107–26, 42129–32, and 44221. We thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A listing of WHI investigators can be found at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. FUSION: This research was supported in part by US National Institutes of Health grants 1-ZIA-HG000024 (to F.S.C.), U01DK062370 (to M.B.), R00DK099240 (to S.C.J.P.), the American Diabetes Association Pathway to Stop Diabetes Grant 1-14-INI-07 (to S.C.J.P.), and Academy of Finland Grants 271961 and 272741 (to M.L.) and 258753 (to H.A.K.). We thank all the subjects for participation and the study personnel for excellent technical assistance. The Pima Indian Study: This study was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, USA. Studies of a Targeted Risk Reduction Intervention with Defined Exercise (STRRIDE): This study was supported by the National Heart Lung and Blood Institute of the National Institutes of Health, HL57453 (WEK). Gene expression in old and young muscle biopsies: S.M. and T.G. were supported in part by NIH U24AG051129. ; Peer Reviewed

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Schubring.'Betriebs‐ und Grundbesitzverhaltnisse der Agrarwirtschaft der Welt', Zeitschrift für Agrargeschichte und Agrarsoziologie, VII (1959), 56‐80.H. Kellenbenz.'Der italienische Grosskaufmann und die Renaissancé, Vierteljahrsschrift für Sozial‐ und Wirtschaftsgeschichte, XXXXV (1958), 145‐167.M. Barkhausen. Staatliche Wirtschaftslenkung und freies Unternehmertum im westdeutschen und im nord‐ und sudniederlandischen Raum bei der Entstehung der neuzeitlichen Industrie im 18. Jahrhundert, Vierteljahrsschrift für Sozial‐ und Wirtschqftsgeschichte, XXXXV (1958), 168‐241.H. Stoob.'Minderstädte. Formen der Stadtentstehung im Spatmittel‐alter', Vierteljahrsschrift für Sozial‐ und Wirtschqftsgeschichte, XXXXVI (1959), 1‐28K. E. Born. 'Sozialpolitische Probleme und Bestrebungen in Deutschland von 1848 bis zur Bismarckschen Sozialgesetzgebung', Vierteljahrsschrift für Sozial‐ und Wirtschqftsgeschichte, XXXXVI (1959), 29‐44.W. Kollmann.'Industrialisierung, Binnenwanderung und "Soziale Frage". (Zur Entstehungsgeschichte der deutschen Industriegroßstadt im 19. Jahrhundert)', Vierteljahrsschrift für Sozial‐ und Wirtschqftsgeschichte, XXXXVI (1959), 45‐70.W. Treue.'Die Ilseder Hütte und der Staat in den Jahren 1916 bis 1919′, Tradition, ZeitschriftfurFirmengeschichte und Untemehmerbiographie, III (1958), 129‐140.P. E. Schramm.'Kaufleute während Besatzung, Krieg und Belagerung (1806‐1815). Der Hamburger Handel in der Franzosenzeit, dargestellt an Hand von Firmen‐ und Familienpapieren', Tradition, Zeitschrift für Firmengeschichte und Untemehmerbiographie, IV (1959), 1‐22 and 88‐114.E. v. BÖVENTER.'Die wirtschaftlichen Auswirkungen amerikanischer Rezes‐sionen auf die iibrige Welt. Eine Untersuchung über die amerikanischen Konjunkturriickschlage, 1937/38, 1949 und 1953/54′, ‐zeitschrift für die p&amte Staatswissenschaft. CXIV (1958). 297‐330.H. 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As Russia's war in Ukraine approaches its two-year anniversary, President Vladimir Putin has reportedly had his suggestions of ceasefire rejected by Washington. On Tuesday, Reuters reported that Russia had approached the United States through intermediaries in late 2023 and early 2024 to propose freezing the conflict along the current lines. Washington reportedly turned down the suggestion, saying that they were not willing to engage in talks if Ukraine was not a participant."Putin was proposing to freeze the conflict at the current lines and was unwilling to cede any of the Ukrainian territory controlled by Russia, but the signal offered what some in the Kremlin saw as the best path towards a peace of some kind," according to Reuters, which cites three anonymous Russian sources. The plan, one of the sources told Reuters, was for national security adviser Jake Sullivan to meet with the Russian counterpart to hash out the details. But after meeting with other senior officials including Secretary of State Antony Blinken and CIA Director Bill Burns, "Sullivan told Ushakov that Washington was willing to talk about other aspects of the relationship but would not speak about a ceasefire without Ukraine, said one of the Russian sources," according to Reuters. Ukrainian President Volodymyr Zelensky has repeatedly said that there is no point in negotiating with Putin and has maintained that he will never accept Russia controlling any part of Ukraine."Everything fell apart with the Americans," one of the sources told Reuters, saying that Washington did not want to pressure Kyiv into reaching an agreement. The sources also added that given the U.S. reaction to a potential ceasefire, Moscow saw little reason to reach out again. Both Washington and Moscow have denied the reporting. The Kremlin "never made any kind of proposal to us nor have we seen any signs that Putin is sincerely interested in ending the war," an unnamed U.S. official told Politico's NatSec daily on Tuesday. Kremlin spokesperson Dmitry Peskov told reporters on Wednesday that the report that Russia had made such an offer was "not true." Despite Washington's insistence, this is the latest piece of evidence that Putin may have pursued a ceasefire in recent months. The New York Times reported late in 2023 that the Russian president had quietly been sending signals to the West that he was prepared to freeze the conflict. "The signals come through multiple channels, including via foreign governments with ties to both the United States and Russia," the Times reported. "Unofficial Russian emissaries have spoken to interlocutors about the contours of a potential deal that Mr. Putin would accept, American officials and others said." The report also revealed that Putin had been interested in a potential ceasefire as far back as the fall of 2022, following Ukraine's successful counteroffensive. As journalist Leonid Ragozin explained in al-Jazeera earlier this week, this may be an effort to pressure the West to negotiate on Putin's terms."What Putin is trying to achieve is making the West face its moral dilemma which boils down to the cost and benefit of resisting his aggression," Ragozin writes. "The continued support for Ukraine's military effort will cost thousands of lives and devastate Ukraine even further, while success is hardly guaranteed." In other diplomatic news related to the war in Ukraine:— The prospects for the next tranche of U.S. aid for Ukraine saw the first glimmer of optimism in months, but the chances that it becomes law remain murky. After a tumultuous negotiation, the Senate passed the $95 billion national security supplemental, which includes approximately $60 billion for Kyiv. The legislation next goes to the House of Representatives, which has been more skeptical of sending aid, and where leadership so far appears unwilling to bring the bill to the floor. Supporters believe that if the House voted on the package, it would pass overwhelmingly, and some have floated pursuing legislative maneuvers that would allow them to supersede leadership and bring the legislation to a vote. — Secretary of State Antony Blinken said he spoke with Paul Whelan, the U.S. Marine currently detained in Russia, on Monday, according to CNN. Blinken provided few details on his conversation with Whelan, who has been detained since December 2018. When asked about a possible prisoner exchange involving Whelan or detained Wall Street Journal reporter Evan Gershkovich, the Kremlin said that such matters could only be resolved, "in silence." — French President Emmanuel Macron announced in a statement that he will sign a bilateral security agreement with Ukraine on Friday. Macron did not specify what exactly the agreement will look like, but he said earlier this year that he was expecting to model an agreement after the 10-year deal that the United Kingdom and Ukraine signed earlier this year. — The Netherlands will join a coalition of countries that is providing Ukraine with advanced drones, according to Reuters. "Ukraine intends to manufacture thousands of long-range drones capable of deep strikes into Russia in 2024 and already has up to 10 companies working on production, Ukraine's digital minister, Mykhailo Fedorov, said in a Reuters interview on Monday."U.S. State Department news:In a Wednesday press briefing, State Department spokesman Matthew Miller reiterated the importance of Congress passing the supplemental, stressing that it was in the national security interest of Ukraine, Europe, and the United States."A lot of that money is spent here, helps develop the manufacturing base here in the United States. And so we will continue to push for the passage of the supplemental bill, and ultimately we think – as the President said, the world is watching," Miller said. "And certainly I'm sure that when we are in Munich we will hear directly from foreign leaders that they are watching very much what Congress does. We know the Ukrainian people are watching. And as the President said, history is watching as well."

Von 1990 bis 2016 wurden in Deutschland mehr als 4,4 Millionen Asylanträge gestellt. Da- von waren es in den Jahren 2015 und 2016 über 1,2 Millionen Anträge. Dieser rapide An- stieg stellte sowohl für die Politik als auch für das Gesundheitssystem eine neue Herausfor- derung dar. Die medizinische Versorgung von Geflüchteten stand bereits im Mittelpunkt verschiedener Forschungsprojekte, beispielsweise in Bielefeld, Bremen, München oder Hal- le. Diese Studien wurden jedoch nicht einheitlich durchgeführt und ermöglichten so nicht immer einen direkten Vergleich. Ähnliches zeigte sich in ausländischen Arbeiten, unter anderem in Belgien, Italien und Malta. Generell findet in Deutschland nach der Ankunft eines Flüchtlings eine Erstuntersuchung statt, die bundeseinheitlich grundlegende Untersuchungen enthält, aber auch länderspezifi- sche Unterschiede aufweist. Da die Befunde der Untersuchungen den Patienten nicht im- mer mitgegeben werden, kann es vorkommen, dass nach einer Verlegung innerhalb Deutschlands dieselben Untersuchungen nochmals durchgeführt werden. Den Zahlen des Bundesamtes für Migration und Flüchtlinge nach handelte es sich bei den Asylbewerbern vorwiegend um Männer (> 65%) und über 70% der Geflüchteten waren weniger als 30 Jahre alt. Sie kamen zum überwiegenden Teil aus Syrien (34,71%), Afghanistan (12,53%) und dem Irak (9,81%). Die Patientendaten für die vorliegende Studie wurden retrospektiv aus dem Kranken- hausinformationssystem der Universitätsmedizin Göttingen, auf Grundlage der hinterleg- ten Kostenträger Sozialamt, Landesaufnahmebehörde, Jugendämter und die Landeswohl- fahrtsverbände generiert. Das untersuchte Patientenkollektiv enthielt Patienten, die unter das Asylbewerberleistungsgesetz fielen. Insgesamt wurden 3.814 Krankenhausfälle mit ei- nem Aufnahmezeitpunkt zwischen November 2014 bis Juli 2016 analysiert, die wiederum in ambulant und stationär sowie in Kinder und Erwachsene aufgeteilt wurden. Die unter- suchten Parameter waren Alter, Geschlecht, Diagnosekategorie nach ICD-10, Klinik, Erlö- se sowie das Herkunftsland. In den Ergebnissen dieser Arbeit wurden 1.634 stationäre und 2.180 ambulante Fälle aus- gewertet. Es zeigte sich, dass die meisten Aufnahmen zwischen September 2015 und Feb- ruar 2016 stattgefunden haben. Die Verteilung des Geschlechts mit ca. 55% männlicher und 45% weiblicher Patienten war sowohl bei den ambulanten als auch bei den stationären Behandlungen zu finden. Ähnliches gilt für die Verteilung des Alters, wobei es sich mit Zusammenfassung 59 ca. 70% vorwiegend um Patienten handelte, die das 30. Lebensjahr noch nicht vollendet hatten. Die Diagnosen unterschieden sich zwischen den ambulanten und stationären Aufnahmen. Bei den ambulanten Fällen handelte es sich zumeist um "Verletzungen, Vergiftungen und bestimmte andere Folgen äußerer Ursachen" und "Krankheiten des Atmungssystems", wohingegen bei den stationären Fällen vorwiegend die Diagnosekategorien "Schwanger- schaft, Geburt und Wochenbett" und "Psychische und Verhaltensstörungen" auftraten. Die Erlöse für die Behandlung der Flüchtlinge beliefen sich über den untersuchten Zeit- raum auf ca. 5.208.801 €. Eine genaue Bestimmung der Erlöse war nur eingeschränkt mög- lich, da es keine detaillierte Aufschlüsselung der Erlöse im ambulanten Bereich gab. Bei der Analyse der Herkunftsländer wurde festgestellt, dass bei ca. einem Viertel des untersuchten Patientenkollektivs keine Staatsbürgerschaft hinterlegt war. An zweiter und dritter Stelle standen Syrien (18,49%) und Afghanistan (10,59%). Das Flüchtlingsthema stellt weiterhin eine Herausforderung für die Gesellschaft dar. Ein wichtiger Punkt ist die noch unzureichende Datenlage über die Gesundheitsversorgung der Flüchtlinge. Eben diese Lücke gilt es zu schließen, um eine evidenzbasierte medizinische Versorgung von Flüchtlingen zu gewährleisten. Weitere Punkte, die in Zukunft angespro- chen werden müssen, sind sowohl die Kommunikation mit den Geflüchteten als auch der bisher noch eingeschränkte Zugang zum Gesundheitssystem, welcher in der Vergangenheit zu erhöhten Kosten geführt hat. In mehreren Studien konnte gezeigt werden, dass bisher von Flüchtlingen keine Gefährdung für die Allgemeinheit ausging. Neben Verletzungen und Atemwegserkrankungen spielen vor allem psychische Erkrankungen eine Rolle. Die in dieser Arbeit gefundenen Ergebnisse decken sich mit den Ergebnissen in der Literatur. ; Between 1990 and 2016, more than 4.4 million people applied for asylum in Germany. There were over 1.2 million applications in 2015 and 2016. This rapid increase posed a new challenge for both politics and the health system. Medical care for refugees has already been the focus of various research projects, for example in Bielefeld, Bremen, Munich and Halle. However, these studies were not carried out uniformly and therefore did not always allow a direct comparison. The same was found in work abroad, including in Belgium, Italy and Malta. In general, an initial examination takes place after the arrival of a refugee in Germany, which includes standard national examinations, but also differs depending on the federal state in which they are conducted. Since the results of the examinations are not always passed on to the patient, sometimes the same examinations are carried out again after a transfer within Germany. According to the figures from the Federal Office for Migration and Refugees, most of the asylum seekers were men (> 65%) and over 70% of the refugees were less than 30 years old. Most of them came from Syria (34.71%), Afghanistan (12.53%) and Iraq (9.81%). The patient data for the present study was generated retrospectively from the hospital information system of the University Medical Center Göttingen, based on the funding agencies: social welfare office, state admission authority, youth welfare offices or the state welfare associations. The patient collective examined contained patients who fell under the Asylum Seekers Benefits Act. A total of 3.814 hospital cases with an admission time between November 2014 and July 2016 were analyzed, which in turn were divided into outpatient and inpatient as well as into children and adults. The parameters examined were age, gender, diagnostic category according to ICD-10, clinical situation, income and the country of origin. In the results of this study, 1.634 inpatient and 2.180 outpatient cases were examined. It turned out that most of the admissions took place between September 2015 and February 2016. The distribution of the sex with approx. 55% male and 45% female patients was found in both outpatient and inpatient treatments. The same applies to the distribution of age, which shows approx. 70% of the patients had not yet reached the age of 30. The diagnoses differed between the outpatient and inpatient admissions. The outpatient cases were mostly "injuries, poisoning and certain other consequences of external causes" and "diseases of the respiratory system", whereas in the inpatient cases the diagnosis categories "pregnancy, childbirth and the puerperium" and "mental and behavioral disorders" were most frequent. The revenues from the treatment of the refugees amounted to approx. € 5.208.801 over the period examined. An exact determination of the revenues was only possible to a limited extent as there was no detailed breakdown of the revenues in the outpatient area. When analyzing the countries of origin, it was found that around a quarter of the examined patient collective had no citizenship on file. Second and third were Syria (18.49%) and Afghanistan (10.59%). The refugee issue continues to be a challenge for society. An important point is the still inadequate data on the health care of refugees. It is precisely this gap that needs to be closed in order to guarantee evidence-based medical care for refugees. Further points that need to be addressed in the future are both communication with the refugees and the previously restricted access to the health system, which has led to increased costs in the past. Several studies have shown that refugees have not posed any health threats to the general public so far. In addition to injuries and respiratory diseases, mental illnesses play a major role. The results found in this work coincide with the results in the literature. ; 2021-04-20

Die pädagogischen Ideen von Jan Amos Komenský/Comenius begründen sich ausgehend von seinem pädagogischen Leitmotiv, als Emblem mit lateinischer Aufschrift auf dem Titelblatt des Buches Comenius, Johann Amos: Orbis sensualium pictus. In lateinischer Sprache lautet das pädagogische Leitmotiv von Jan Amos Komenský/Comenius "Omnia sponte fluant, absit violentia rebus!", in deutscher Sprache "Alles fließe von selbst, Gewalt sein ferne den Dingen!". Die pädagogischen Ideen von Jan Amos Komenský sind in der Tschechischen Republik lebendig, seine literarischen Schriften, vor allem sein Roman "Labyrint sveta a raj srdce" Labyrinth der Welt und Paradies des Herzens" werden im Literaturunterricht am Gymnasium gelesen, damit werden seine Gedanken, Ideen und Zukunftsperspektiven an tschechische Schüler und Schülerinnen vermittelt. Die Institutionen Národní pedagogické muzeum a knihovna JA Komenského Praha, Gedenkstätte Fulnek, das Muzeum Jan Amos Komenského Přerov und das Muzeum Jan Amos Komenského Uherský Brod gestalten die Erinnerung an den Pädagogen Komenský/Comenius durch Ausstellungen, Konzerte und Tagungen und bieten Pädagogische Weiterbildungen für Lehrer und museumspädagogische Erlebnisprogramme für Schüler. Das Schul- und Bildungswesen der Niederlande orientiert sich an den pädagogischen Ideen von Jan Amos Komenský/Comenius. Die pädagogische Wertschätzung von Comenius in den Niederlanden wird deutlich durch die Einführung eines neuen fälschungssicheren Schuldiploms durch das Ministerium für Bildung, Kultur und Wissenschaft mit dem Stellenwert eines Zeugnisses für den Hochschulzugang. Als Schuldiplom für den voruniversitären Bildungsgang zur Aufnahme an einer niederländischen Universität besitzt das Zeugnis mit den Porträtabbildungen von Jan Amos Komenský/Comenius, Hugo Grotius und Baruch de Spinoza einen hohen Stellenwert. Durch die gute Verbundenheit mit dem tschechischen Gelehrten Jan Amos Komenský/Comenius und durch die Drucklegung seiner pädagogischen Werke in Deutschland, besteht für das deutsche Schul- und Bildungswesen ein kontinuierlicher Gedankenaustausch zur Erforschung und Anwendung der pädagogischen Ideen von Jan Amos Komenský/Comenius. Die Deutsche Comenius Gesellschaft vollzieht in ihren Tätigkeiten, Aufgaben, Veröffentlichungen und Veranstaltungen den Auftrag, die pädagogischen Ziele des tschechischen Gelehrten, Theologen, Philos- Bernhard Josef Stalla 188 ophen und Pädagogen Jan Amos Komenský/Comenius zu verwirklichen. Ein zentrales Anliegen des Comenius-Expertenforum an der Ludwig-Maximilians-Universität München besteht darin, den aktuellen Europäischen Bildungsauftrag hinsichtlich seiner historischen Grundlagen und der von Comenius erarbeiteten geistig-politischen Wurzeln des Europäischen Bildungsgedankens offenzulegen und professionell zu fördern. Die Comenius-Forschungsstelle an der AlanisHochschule Alfter und die ihr zugehörige Forschungsbibliothek.versteht sich in erster Linie als eine wissenschaftliche Forschungseinrichtung, weiß sich aber auch dem kulturellen Erbe des Comenius verpflichtet ; Idee edukacyjne Jana Amosa Komeńskiego / Comeniusa można podsumować w duchu strony tytułowej jego książki Orbis sensualizm pictus. Edukacyjną myślą przewodnią Jana Amosa Komeńskiego / Comeniusa jest Omnia sponte fluant, absit violentia rebus! ("Wszystkie rzeczy płyną spontanicznie, jeśli nie ma przemocy!"). Idee edukacyjne Jana Amosa Komeńskiego w Czechach są żywe, jego pisma literackie, a zwłaszcza jego powieść Labyrint świata a raj serca, czytane są na lekcjach literatury w gimnazjum, aby jego myśli, idee i perspektywy były przekazywane czeskim uczniom i studentom. Państwowe Muzeum Pedagogiczne im. Jana Amosa Komeńskiego w Pradze, Memoriał Fulnek, Muzeum Jan Amosa Komeńskiego w Przerowie i Muzeum Jana Amosa Komeńskiego w Uherskim Brodzie pielęgnują pamięć o pedagogu Komeńskim / Comeniusie poprzez wystawy, koncerty i konferencje oraz zapewniają szkolenie edukacyjne dla nauczycieli i muzealne programy praktyk edukacyjnych dla studentów. System edukacji w Holandii opiera się na pedagogicznych ideach Jana Amosa Komeńskiego/ Comeniusa. Pedagogiczne uznanie dla Komeńskiego w Holandii wzrosło dzięki wprowadzeniu przez Ministerstwo Edukacji, Kultury i Nauki nowego dyplomu ukończenia szkoły zabezpieczonego przed fałszerstwami certyfikatem z portretem Jana Amosa Komeńskiego / Comeniusa. Dyplomy z portretami Komeńskiego, Hugo Grotiusa i Barucha de Spinozy mają wysoki priorytet. Dzięki dobrym relacjom z czeskim naukowcem Janem Amosem Komeńskim / Comeniusem oraz publikacją jego dzieł edukacyjnych w Niemczech, istnieje ciągły dialog koncepcji badań i zastosowanie idei pedagogicznych Jana Amosa Komeńskiego / Comeniusa w edukacji szkolnej w Niemczech. Niemieckie Towarzystwo Komeńskiego w Berlinie organizuje działania, zadania, publikacje i wydarzenia, aby osiągnąć edukacyjne cele Komeńskiego. Główną ideą Forum Comenius-Expert na Uniwersytecie Ludwika Maksymiliana jest obecny europejski porządek edukacyjny w zakresie historycznych, teologicznych, filozoficznych i pedagogicznych idei Jana Amosa Komeńskiego. Polityczne korzenie europejskiego myślenia o edukacji wpłynęły na przygotowanie mentalne w kierunku uświadomienia oraz promowania międzynarodowej współpracy dla pokojowego świata bez granic. Centrum Badawcze Comeniusa na Alanus-University w Alfter i związana z nim badaniami Biblioteka Badawcza Komeńskiego zgłębiają zagadnienia związane z życiem, pracą i wpływem Jana Amosa Komeńskiego (*1592-†1670) w kontekście nowożytnego rozwoju, ale także dziedzictwa kulturowego Jana Amosa Komeńskiego dzisiaj. ; The educational ideas of John Amos Komenský/Comenius can be summarized in the motif of the title page of his book Orbis sensualium pictus. In the Latin language, the educational keynote of John Amos Komenský/Comenius is "Omnia sponte fluant, absit violentia rebus!", in the English language, "All things flow spontaneously, if violence is absent!". The educational ideas of Jan Amos Komenský in the Czech Republic are alive, his literary writings, especially his novel "Labyrintsveta a raj srdce" are read in literature classes at secondary school, so that his thoughts, ideas and perspectives are conveyed to Czech pupils and students. The National Pedagogical Museum of John Amos Comenius in Prague, the Memorial Fulnek, the Museum of John Amos Comenius in Přerov and the Museum of Jan Amos Comenius in Uherský Brod keep the memory of the pedagogue Komenský/Comenius alive through exhibitions, concerts and conferences, and provide educational training for teachers and Museum educational experience programs for students. The School and education system in the Netherlands is based on the pedagogical ideas of John Amos Komenský/Comenius. The pedagogical appreciation of Comenius in the Netherlands was promoted through the introduction of a new tamper-proof school diploma by the Ministry of education, culture and science, with the importance of a high school certificate. As a school diploma of pre-university education, when submitted for admission to a Dutch University, the certificate with portrait illustrations of John Amos Komenský/Comenius, Hugo Grotius and Baruch de Spinoza has a high priority. By the good relationship with the Czech scientist John Amos Komenský/Comenius and by the publication of his educational works in Germany, there is a continuous dialogue of ideas for the research and application of the pedagogical ideas of Jan Amos Komenský/Comenius for the school education in Germany. The German Comenius Society in Berlin organizes activities, tasks, publications and events in order to achieve the educational intentions of Komenský/Comenius. A central idea of the Comenius-Expert Forum at the LudwigMaximilians-University of Munich is the current European education order in terms of its historical foundations, and of the theologian, philosopher and pedagogue John Amos Comenius, political roots of the European thinking of education prepared mentally to be disclosed, and to promote international cooperation for a peaceful world without borders. The Comenius Research Centre at the Alanus-University in Alfter and the associated Comenius Research Library explore the issues of life, work and influence of John Amos Comenius (*1592-†1670) in the context of early modern development, but also of the cultural heritage of Comenius today.

In der vorliegenden Arbeit wurden Leben und Werk des Bergbauingenieurs, Unternehmers, Mäzens und Mineraliensammlers Dr. Richard Baldauf (1848-1931) untersucht und in einen wissenschaftshistorischen Zusammenhang gebracht. Eine Neubearbeitung der Biografie von Richard Baldauf (1848-1931) förderte interessante Details, besonders in Zusammenhang mit den politischen und wirtschaftlichen Umständen der damaligen Zeit, zutage. Die Bearbeitung von Mineralproben aus seiner Sammlung zeigt die Entwicklungen und Fortschritte im Wissenschaftszweig Mineralogie innerhalb der letzten 100 Jahre auf. Julius Richard Baldauf wurde am 09. März 1848 in Chemnitz geboren. Nach erfolgreichem Abschluss seines Bergbauingenieurstudiums im Jahr 1869 blieb Baldauf weiterhin als bergmännischer Kurspraktikant an der Königlich-Sächsischen Bergakademie Freiberg eingeschrieben, um den Grad eines Markscheiders zu erhalten. Es folgten Anstellungen im damals tiefsten Kohlenschacht Deutschlands "Frisch Glück" in Oelsnitz (1871-1874) und beim Hänichener Steinkohlenbauverein (1874-1876). Die böhmische Braunkohle machte der sächsischen Steinkohle gegen Ende des 19. Jahrhunderts allmählich Konkurrenz. Sie kam bereits im Jahr 1880 auf sechs Eisenbahnlinien und auf der Elbe nach Sachsen. Später breitete sich ihr Einsatz auf das gesamte Deutsche Kaiserreich aus. Diese wirtschaftliche Gunst wurde auch von Richard Baldauf erkannt. Er siedelte mit seiner Ehefrau Rosalie (geb. Rudolph, 1855-1918) und seinen Kindern nach Nordwestböhmen über, um im Braunkohlenbergbau tätig zu werden. Baldauf nahm zunächst Anstellungen als Bergverwalter in Klostergrab (Hrob) und als Bergdirektor in Ladowitz (Ledvice) an, bis es 1891 in Gemeinschaft mit seinem Schwager Hermann Eduard Rudolph (1846- ?) zur Gründung der Baldauf-Rudolphschen Braunkohlenwerke kam, die ihren Hauptsitz in Dux (Duchcov) hatten. Das Baldauf-Rudolphsche Braunkohlenwerk erwarb im Laufe der Jahre mehrere Grubenfelder, u. a. die Grube Hermann in Sobrusan (Zabrušany), Grube Richard in Brüx (Most) und die Grube Marianne in Skyritz (Skyřice). Im Jahr 1913 besaß der Betrieb insgesamt 20 Gruben im nordwestböhmischen Braunkohlenrevier. Richard Baldauf war ein fortschrittlich denkender und technisch interessierter Mensch. So wollte er bereits im Jahr 1883 moderne Abraummaschinen aus England in Böhmen einführen. Sein fortschrittliches Denken führte auch dazu, dass er mit der Grube Richard in Brüx (Most) einen wirtschaftlichen Tagebaubetrieb schuf. Dieser zählte zu den technisch modernsten Anlagen im Revier. Der Mitbegründer des Baldauf-Rudolphschen Braunkohlenwerks war der Architekt Hermann Eduard Rudolph. Er schloss sein Studium an der Kunstakademie Dresden im Jahr 1872 ab, um anschließend als Baumeister und Architekt in Teplitz (Teplice) zu wirken. Dass Hermann sehr erfolgreich war, zeigte er beim Bau der Teplitzer Synagoge, denn hier wurden seine Baupläne umgesetzt. Martin Baldauf, einziger Sohn von Richard und Rosalie Baldauf, sollte auch Bergbau in Freiberg studieren, um später die Geschäfte im väterlichen Braunkohlenwerk fortführen zu können. Er übernahm ab dem Jahr 1908 im Verwaltungsgebäude des Hermannschachts in Dux (Duchcov) die kaufmännischen Arbeiten. Durch die erfolgreiche Unternehmertätigkeit im böhmischen Braunkohlenrevier ist die Familie Baldauf zu Wohlstand gekommen. Mit diesem finanziellen Hintergrund war es Richard Baldauf möglich, ab dem Jahr 1904 eine wertvolle Mineraliensammlung aufzubauen und als Mäzen der Geowissenschaften in Sachsen hervorzutreten. Im Laufe von 25 Jahren hatte er 10 000 Mineralstufen zusammengetragen. Die in vier Teilkollektionen gegliederte Sammlung legte er nach wissenschaftlichen Gesichtspunkten an. In seinem "Öffentlichen Mineralogischen Museum", welches er auf der Geinitzstraße 5 in Dresden im Jahr 1916 eröffnete, präsentierte er unentgeltlich seine eindrucksvollen Mineralstufen. Der erfolgreiche Fortbestand des Braunkohlenunternehmens war nach dem Ersten Weltkrieg nicht mehr möglich, da nach Kriegsende eine politische Neuordnung in Europa entstand. Das führte im Jahr 1920 zwangsläufig zum Verkauf der Baldaufschen Gruben in Böhmen an die Tschechische Handelsgesellschaft. Mit dem Anteil des Erlöses aus dem Braunkohlenwerk wagte Richard Baldaufs Sohn Martin einen Neuanfang als Schokoladenfabrikant in Braunschweig, da Lebens- und Genussmittel nach dem Ersten Weltkrieg dringend benötigt wurden. Aufgrund der hohen Konkurrenz in dieser Branche, der zunehmenden Geldentwertung und eintretenden Weltwirtschaftskrise im Jahr 1929 bekam die Familie Baldauf, wie viele andere Familien auch, finanzielle Probleme. Die Fortführung des neugegründeten Unternehmens war nun nicht mehr möglich. Richard Baldauf wollte seinem Sohn aus der finanziellen Krise heraushelfen. So hegte er den Gedanken, seine wertvolle Sammlung zu verkaufen. Aus diesem Grund sind in den Jahren 1929 und 1930 zahlreiche Verkaufsverhandlungen im In- und Ausland durchgeführt worden, die aber erfolglos blieben. Der Verkauf der geschlossenen Sammlung wurde erst im Jahr 1939 durch Baldaufs Erben möglich. Im Zeitraum 1904 bis 1929 war Richard Baldauf mit dem Aufbau seiner Mineraliensammlung beschäftigt und wurde als Mäzen in Sachsen aktiv. Baldauf war vor allen in Fachkreisen für seine Großzügigkeit und seinen Einsatz als Förderer bekannt. Er ermöglichte dem Museum für Mineralogie und Geologie Dresden, dem Mineralogisch-Geologischen Institut der TH Dresden, der Bergakademie Freiberg und dem dortigen Institut für Geologie und Lagerstättenlehre die Anschaffungen wertvoller Minerale, teilweise ganzer Sammlungen sowie wissenschaftlicher Instrumente. An dieser Stelle ist die Baldauf-Stiftung in Höhe von 1 Million Mark aus dem Jahr 1920 besonders hervorzuheben. Diese Summe stammte aus dem Verkauf des Baldauf-Rudolphschen Braunkohlenwerkes und sollte der TH Dresden zu Unterstützungszwecken dienen. Im Rahmen der Dissertation wurde ein Teil der mineralogischen Sammlung von Richard Baldauf neu bearbeitet und in einen wissenschaftshistorischen Zusammenhang gestellt. Zunächst werden die Methoden zur Mineralidentifizierung in der Ära Baldauf vorgestellt sowie mineralogische Einteilungssysteme, die er für seine Sammelarbeit genutzt hat. Diskutiert wird weiterhin die heutige Systematik und Benennung von Mineralen, womit zu den Revisionsarbeiten übergeleitet wird. Im Rahmen der Dissertation wurden 25 Proben aus der Sammlung Baldauf mittels Röntgendiffraktometrie (XRD), Rasterelektronenmikroskopie (REM) gekoppelt mit einer energiedispersiven Elektronenstrahlmikroanalyse (ESMA oder EDS) und Thermoanalyse (DTA-TG-DTG) einer Revision unterzogen. Minerale, die in Baldaufs Sammelära noch völlig unbekannt waren, Fehlbestimmungen, Gemenge oder Minerale, die zuvor noch keiner Untersuchung unterzogen worden sind, konnten vollständig geklärt werden. Die aktuell ermittelten Untersuchungsergebnisse sind in 17 Fällen eindeutig, sieben Proben konnten nur teilweise geklärt werden. Für eine Mineralprobe konnte gar kein Ergebnis mit den modernen, mineralogischen Untersuchungsverfahren erzielt werden. Die Mineralproben, bei denen eine vollständige Identifizierung nicht möglich war, sollten einer nochmaligen Präparation und Untersuchung unterzogen werden. Die gründliche Aufarbeitung der gesamten Sammlung Baldauf würde mehrere Jahre in Anspruch nehmen. Die Revisionsarbeiten bieten noch sehr viel Potenzial, das von der wissenschaftlichen Gemeinschaft in Zukunft verstärkt in Kooperation genutzt werden sollte. Auch Baldaufs umfangreicher archivalischer Nachlass konnte im Rahmen der Dissertation inhaltlich nicht vollständig bearbeitet werden. Bei einer weiteren Untersuchung würden vermutlich noch mehr interessante Details hervortreten. Da im archivalischen Nachlass nur die Briefe und Rechnungen enthalten sind, die Baldauf selbst empfangen hat, ist davon auszugehen, dass sich noch weitere, von ihm verfasste Schriftstücke, in anderen Institutionen auffinden lassen. So lassen sich beispielsweise über den Verbundkatalog für Nachlässe und Autografen "Kalliope" vier Briefe von Richard Baldauf an den Münchner Mineralogen Paul Heinrich Groth in der Bayerischen Staatsbibliothek München nachweisen. Baldaufs Abschlussarbeit an der Königlich-Sächsischen Bergakademie Freiberg aus dem Jahr 1869 war im Universitätsarchiv Freiberg nicht mehr aufzufinden. Nach dem Zweiten Weltkrieg sind dort zahlreiche Akten vernichtet worden. Wenig überliefert bleiben Details zu Baldaufs Tätigkeiten im sächsischen Steinkohlenrevier (Frisch-Glück-Schacht in Oelsnitz, Hänichener Steinkohlenbauverein). Das liegt vermutlich darin begründet, dass Baldauf nur wenige Jahre dort tätig gewesen ist. Abschließend ist festzustellen, dass die Sammlung Baldauf für die Sammlungsdokumentation, für die mineralogische und wissenschaftshistorische Forschung im angegebenen Zeitraum auch in Zukunft vielfältige Forschungsansätze bietet. ; This work investigated life and work of the mining engineer, entrepreneur, patron and mineral collector Dr. Richard Baldauf (1848-1931) and brought it into a scientifically historical context. A new revision of Richard Baldauf´s biography made appear interesting details, especially concerning the political and economical conditions of his time. The examination of mineral samples of his collection shows how the scientifical branch of mineralogy has developed and improved during the last 100 years. Julius Richard Baldauf was born on 9th March 1848 in Chemnitz. After having finished successfully his studies of mining science in 1869, Baldauf remained enroled at the Mining Academy Freiberg as a mining trainee, in order to achieve the title of a mine surveyor. Afterwards he was employed from 1871 to 1874 at "Frisch Glück" at Oelsnitz, which at that time was the deepest coal mine of Germany, and at "Hänichener Steinkohlenbauverein" (1874-1876). Towards the end of the 19th century the Bohemian brown coal started becoming a rival product for the Saxon hard coal. Already in 1880, it was transported into Saxony via six railway lines and the river Elbe. Later it was used more widely, in the complete German Empire. Among others, Richard Baldauf recognised this economical chance. He moved with his wife Rosalie (née Rudolph, 1855-1918) and their children to the northwest of Bohemia to work in the brown coal mining. In the beginning Baldauf became employed as a mining administrator in Klostergrab (Hrob) and as a mining director in Ladowitz (Ledvice), until he founded with his brother-in-law, Hermann Eduard Rudolph (1846- ?), the so-called "Baldauf-Rudolphsche Braunkohlenwerke", which had its main base in Dux (Duchcov). The "Baldauf-Rudolphsches Braunkohlenwerk" bought, as the years went by, some mining fields, among them the mine Hermann at Sobrusan (Zabrusany), mine Richard at Brüx (Most) and the mine Marianne at Skyritz (Skyrice). In 1913 the company possessed all in all 20 mines in the brown coal region in the northwest of Bohemia. Richard Baldauf was a man who was interested in progress and technology. No later than in 1883 he wanted to introduce modern machines from England into Bohemia. These machines were designed to remove the mining waste. His modern manner of thinking lead also to his creating the mine Richard at Brüx (Most) as an economically-working mining factory. It was counted among the region´s most modern constructions. Co-founder of the "Baldauf-Rudolphsches Braunkohlenwerk" was the architect Hermann Eduard Rudolph. He had finished his studies at the Kunstakademie Dresden in 1872, afterwards he became constructor and architect in Teplitz (Teplice). His construction plans were made reality in the building of the Teplitz synagogue. That demonstrates impressively how successful Hermann was. Martin Baldauf, only son of Richard and Rosalie Baldauf, was encouraged to study mining at Freiberg, too, in order to succeed his father later as administrator of their coal-mining company. From 1908 on he did the economical work at the administrational building of the Hermann-shaft at Dux (Duchcov). Being successful entrepreneurs in the Bohemian brown coal mining region meant for the Baldauf family living in prosperity. This financial background helped Richard Baldauf to establish, from 1904 on, a valuable collection of minerals and to made himself known as patron of the geological sciences of Saxony. In 25 years he had collected 10 000 mineral specimens. He established his collection according to scientific aspects. It was divided into four sections. In his Public Mineralogical Museum, which he in 1916 opened in Dresden, at Geinitzstraße 5, he presented his impressive mineral specimens without demanding an entrance free. After the First World War, his brown coal mining company could no longer exist successfully, for after the war Europe was politically divided and organised differently. Therefore, the Baldauf mines in Bohemia had to be sold to the Czech Trade Company in 1920. After having been given his share of the proceeds of the brown coal mining company, Richard Baldauf´s son Martin endeavoured a new start as a chocolate entrepreneur at Braunschweig, for after the First World War food and drink were needed urgently, no matter if for every day or semi-luxury. But there was high competition in this field, money was losing its valour increasingly and in 1929 the worldwide economic crisis began. That is why the Baldauf family, like many others, started having financial problems. Now it was not possible to go on with the newly-found enterprise. Richard Baldauf wanted to help his son to emerge of the financial crisis. Therefore, he was thinking of selling his valuable collection. That is why in 1929 and 1930 many sale negotiations took place, all without success. Only in 1939 the heirs of the Baldauf family were able to sell the complete collection. Between 1904 and 1929, Richard Baldauf was establishing his mineral collection and became active in Saxony as a patron. Particularly among specialists and scientists of his field, he was famous for his generosity and his commitment as a patron. He made it possible for the Museum for Mineralogy and Geology Dresden, the Institute for Mineralogy and Geology of the TH Dresden, the Mining Academy Freiberg and its Institute for Geology and Economic Geology to acquire valourable minerals, even as whole collections, and scientific instruments. Furthermore, he sponsored the work of scientific and other assistants. In that context the Baldauf foundation has to be emphasized in particular. It was founded in 1920 with a sum of 1 million Deutschmarks. This money had been earned with the sale of the "Baldauf-Rudolphsches Braunkohlenwerk" and was designed to support the TH Dresden. In this doctoral thesis a part of Richard Baldauf´s mineralogical collection was revised and put into a scientifically historical context. First, the methods for mineral identification in the Baldauf era and mineralogical classification systems that he used for his collection work were presented. Furthermore, the systematization and nomination of minerals that are applied today are discussed. That leads to the revision work. In the doctoral thesis 25 samples from the Baldauf collection were revised, applying X-ray diffraction (XRD), scanning electron microscope (SEM), combined with an energy-dispersive microanalytical spectrometer (EDS) and thermal analysis, including a combination of differential thermal analysis (DTA), thermal gravimetric analysis (TG) and derivative thermogravimetry (DTG). So entire research could be made about minerals that in Baldauf´s times still were totally unknown and minerals that had been classified wrongly or not at all. 17 of the research results made here are definitive, seven samples could only partly be clarified. No result at all could be made for one sample, using the modern, mineralogical examination methods. Those mineral samples for which a complete examination was not possible should be prepared and examined again. To revise the whole Baldauf collection thoroughly would take some years. There is still much potential in the revision work. In the future, that should be used cooperatively even more than today by the scientific community. Baldauf´s wide archival holdings, too, could not be seen through completely in this doctoral thesis as far as its content is concerned. In a second examination probably more interesting details would come to light. Since the archival holdings only contain the letters and receipts that Baldauf himself received, it seems probable that in other institutions further papers can be found the author of which he is. Using the corporal catalogue for heritages and autographers, "Kalliope", four letters can be proven, written by Richard Baldauf to the mineralogist Paul Heinrich Groth, of Munich, of the Bavarian State Library, Munich. Baldauf´s final thesis with the Mining Academy Freiberg, from 1869, was intraceable and could not be found anymore at the University Archive at Freiberg. After the Second World War numerous files have been destroyed there. Few information could be found to details about Baldauf´s work in the Saxon hard coal region (the shaft Frisch-Glück-Schacht in Oelsnitz, the Hänichener Steinkohlenbauverein). The reason might be that Baldauf worked there for only some years. In the end it must be emphasized that it becomes evident that, in the future, too, the Baldauf collection offers numerous research opportunities: for the collection documentation and for the mineralogical and scientifically historical investigation for the said time.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. ; European Innovation Partnership on Active and Healthy Ageing Reference Site MACVIA-France, European Structural and Development Funds of Region Languedoc Roussillon ; Imperial Coll London, Natl Heart & Lung Inst, Royal Brompton Hosp NHS, London, England ; UPMC Paris 06, Sorbonne Univ,Dept Pneumol & Addictol,UMR S 1136, Hop Arnaud de Villeneuve,CHRU Montpellier, IPLESP,Equipe EPAR,Unite Allergol, F-75013 Paris, France ; Univ S Florida, Morsani Coll Med, Tampa, FL USA ; Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Christine Kuhne Ctr Allergy Res & Educ CK CARE, Davos, Switzerland ; Univ Hosp Ghent, ENT Dept, Upper Airways Res Lab URL, Ghent, Belgium ; IQ4U Consultants Ltd, London, England ; Osped Riuniti, Univ Hosp, Allergy Unit, Dept Internal Med, Ancona, Italy ; Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria ; Univ Naples 2, Rome, Italy ; CNR, IFT, Rome, Italy ; Univ Genoa, Allergy & Resp Dis Clin, DIMI, IRCCS AOU San Martino IST, Genoa, Italy ; Hosp Univ Vall dHebron, Allergy Sect, Dept Internal Med, Barcelona, Spain ; Montpellier UPMC Univ Paris 06, Sorbonne Univ,UMRS 1136, Hop Arnaud de Villeneuve,Equipe EPAR IPLESP, Div Allergy,Dept Pulmonol,Univ Hosp Montpellier, Paris, France ; Nova Southeastern Univ, Ft Lauderdale, FL USA ; Univ Hosp Strasbourg, Div Allergy, Chest Dis Dept, Strasbourg, France ; Univ Versailles St Quentin, Suresnes, France ; Foch Hosp, Dept Airway Dis, Clin Pharmacol Unit, UPRES EA 220, Suresnes, France ; Rangueil Larrey Hosp, Dept Resp Dis, Toulouse, France ; Univ Palermo, Di Bi MIS, Palermo, Italy ; Kings Coll London, Guys & St Thomas NHS Trust, London, England ; Imperial Coll London, Natl Heart & Lung Inst, Allergy & Clin Immunol Sect, London, England ; Childrens Hosp, Dept Pediat Pulmonol & Allergy, Aarau, Switzerland ; Bambino Gesu Pediat Hosp, Dept Pediat, Div Allergy, Rome, Italy ; Kings Coll London, Allergy Acad, London, England ; Erasmus MC, Dept Internal Med, Bldg Rochussenstr, Rotterdam, Netherlands ; Hosp San Bernardo, Unidad Alergia & Asma, Salta, Argentina ; Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland ; Odense Univ Hosp, Hans Christian Andersen Childrens Hosp, Odense, Denmark ; Katholieke Univ Leuven, Univ Hosp Leuven, Clin Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium ; Secretary Immunotherapy Interest Grp EAACI, Allergy Learning & Consulting, Copenhagen, Denmark ; UPMC Univ Paris, Sorbonne Univ,Hop Enfants Armand Trousseau,INSERM, Inst Pierre Louis Epidemiol & Sante Publ,Equipe E, Allergol Dept,Ctr Asthme & Allergies,UMR S 1136, Paris, France ; Hosp Sirio Libanes, Sao Paulo, Brazil ; Univ Hosp Montpellier, Montpellier, France ; UPMC Paris 06, Sorbonne Univ, Equipe EPAR, UMR S 1136,IPLESP, Paris, France ; Ackermann Hanf & Kleine Tebbe, Outpatient Clin & Clin Res Ctr, Allergy & Asthma Ctr Westend, Berlin, Germany ; German Soc Otorhinolaryngol HNS, Ctr Rhinol & Allergol, Wiesbaden, Germany ; Univ Med Ctr Utrecht, Dept Immunol & Dermatol Allergol, Utrecht, Netherlands ; Med Univ Lodz, Lodz, Poland ; ARIA, Mexico City, DF, Mexico ; Hosp Med Sur, AAAAI, Mexico City, DF, Mexico ; Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark ; Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark ; Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark ; Charite Med Univ, Pediat Pneumol & Immunol, Berlin, Germany ; Gentofte Univ Hosp, Allergy Clin, Danish Allergy Ctr, Hellerup, Denmark ; Klinikum Univ Koln AoR, IMSIE, Cologne, Germany ; Hosp Clin Barcelona, Unitat Rinol & Clin Olfacte, ENT Dept, Clin & Expt Resp Immunoallergy,IDIBAPS,CIBERES, Barcelona, Catalonia, Spain ; Padua Gen Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr Veneto Reg, Padua, Italy ; Univ Athens, Allergy Unit, Pediat Clin 2, Athens, Greece ; Univ Genoa, Allergy & Resp Dis, IRCCS San Martino IST, Genoa, Italy ; ASST Grande Osped Metropolitano Niguarda, Pzza Osped Maggiore, Milan, Italy ; Univ Med Mannheim, Dept Otorhinolaryngol Head & Neck Surg, Mannheim, Germany ; Heidelberg Univ, Med Fac Mannheim, Heidelberg, Germany ; Ctr Rhinol & Allergol, Wiesbaden, Germany ; Univ Aberdeen, Acad Primary Care, Div Appl Hlth Sci, Primary Care Resp Med, Aberdeen, Scotland ; RiRL, Cambridge, England ; Optimum Patient Care Ltd, Singapore, Singapore ; Hosp Infantil Univ Nino Jesus, Allergy Sect, Madrid, Spain ; Ludwig Maximillian Univ, Dept Dermatol & Allergol, Munich, Germany ; Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland ; Royal Natl Throat Nose & Ear Hosp, London, England ; UCL, London, England ; Univ Zurich Hosp, Clin Trials Ctr, Zurich, Switzerland ; Imperial Coll London, Natl Heart & Lung Inst, Allergy & Clin Immunol Inflammat Repair & Dev Sec, Immunomodulat & Tolerance Grp,Fac Med, London, England ; MRC, London, England ; Asthma UK Ctr Allerg Mechanisms Asthma, London, England ; Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Asthma UK Ctr Appl Res, Med Informat Ctr, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland ; SLAAI, Asuncion, Paraguay ; Univ Fed Sao Paulo, Programa Posgrad Pediat & Ciencias Aplicadas Pedi, Dept Pediat EPM, Sao Paulo, Brazil ; Med Univ Graz, Dept Dermatol & Venerol, Graz, Austria ; Allergy Outpatient Clin Reumannplatz, Vienna, Austria ; Complejo Hosp Navarra, Serv Alergol, Pamplona, Spain ; Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Amsterdam, Netherlands ; Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Amsterdam, Netherlands ; Univ Bari, Sch Med, Unit Geriatr Immunoallergol, Interdisciplinary Dept Med, Bari, Italy ; Complejo Hosp Univ Santiago de Compostela, Dept Allergy, Santiago De Compostela, Spain ; Med Univ Graz, Dept Paediat, Resp & Allerg Dis Div, Graz, Austria ; Charite Univ Med Berlin, Klin Dermatol Venerol & Allergol, Allergie Ctr Charite, Berlin, Germany ; European Innovat Partnership Act & Hlth Ageing Re, MAlad Chron Vleillissement Actif Languedoc Roussi, Paris, France ; INSERM, VIMA, Epidemiol & Publ Hlth Approaches, U1168,Ageing & Chron Dis, Paris, France ; Univ Versailles St Quentin En Yvelines, UVSQ, UMR S 1168, Versailles, France ; CHRU, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France ; Programa de Pòs‑Graduação em Pediatria e Ciências Aplicadas à Pediatria, Departamento de Pediatria EPM, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil ; Web of Science

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today's technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics. © 2019, The Author(s). ; Istanbul Üniversitesi: 3 Istituto Nazionale di Fisica Nucleare Joint Institute for Nuclear Research Istituto Nazionale di Fisica Nucleare CNRS/IN2P3/UPSUD/ LAL University of Oxford INFN CT Kyoto University Kennesaw State University Kangnung National University Joint Institute for Nuclear Research Korea Institute of Toxicology King's College London Islamic Azad University Fondation Louvain CA Chinese Academy of Agricultural Sciences 2 Instituto Nazionale di Fisica Nucleare Kyungpook National University Universidad de Guanajuato High Magnetic Field Laboratory, Chinese Academy of Sciences Nuclear Physics Shenyang Normal University Princeton University, Princeton Stony Brook University: TU Darmstadt University of Tokyo Monash University National and Kapodistrian University of Athens Peking University Trinity College Dublin University of Pittsburgh, Pitt Tsinghua University Universidade do Estado do Rio de Janeiro ES National Research Nuclear University MEPhI Institute for Research in Fundamental Sciences Tel Aviv University Princeton University, Princeton United States Pharmacopeia Tokyo Institute of Technology University of Delhi Tokyo Institute of Technology Technische Universität Dresden: TU Dresden Dalian Institute of Chemical Physics National Rehabilitation Center National Research Center "Kurchatov Institute" Loughborough University Eidgenössische Technische Hochschule Zürich: RWTH Royal Holloway, University of London Trinity College Dublin Scuola Internazionale Superiore di Studi Avanzati Technische Universitat Wien, TU Wien Universidade do Estado do Rio de Janeiro Massachusetts Institute of Technology: MIT Mount Allison University Novosibirsk State Technical University Technische Universität Berlin Pusan National University University of Glasgow National Intelligence University Northwestern University Shahid Beheshti University of Medical Sciences Rutgers, The State University of New Jersey: UNIROMA1 Kingston Technology Nankai University Pennsylvania State University: PSU Royal Holloway, University of London Stanford University Bauman Moscow State Technical University: MSU Florida State University Institute for Research in Fundamental Sciences Lawrence Berkeley National Laboratory, Berkeley Lab Shanghai Jiao Tong University PSI SLAC Natural History Museum University of Chicago University of Cincinnati University of Illinois University of Birmingham University of Cambridge University of California, San Diego University of California, Santa Barbara University of California, Santa Cruz University of Florida City, University of London, City University of California: UCI UCB University College Dublin University of Bristol Health Effects Institute University of California, Santa Barbara University of California, Santa Cruz Sapienza Università di Roma: UNIROMA1, UNIROMA2, UNIROMA3 University of Illinois at Urbana-Champaign Universidade Federal do Rio de Janeiro Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya: UCL, UC, TW, TU, UA University of California, Irvine: UCSD Università degli Studi di Firenze University of California Berkeley, UC Berkeley University of Arizona Secrétariat Général pour les Affaires Régionales, Etat en Région Aquitaine Secrétariat Général pour les Affaires Régionales, Etat en Région Aquitaine École Polytechnique Fédérale de Lausanne Bundesamt für Energie Seventh Framework Programme: 312453, EuCARD-2 777563, 730871, 654305 European Synchrotron Radiation Facility European Synchrotron Radiation Facility ; 111 Istanbul Aydin University (IAU), Istanbul, Turkey 112 Istanbul University (IÜ), Istanbul, Turkey 113 Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Salerno – Sezione di Napoli (INFN SA), Salerno, Italy 114Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Gran Sasso (INFN LNGS), Assergi (L'Aquila), Italy 115Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Frascati (INFN LNF), Frascati, Italy 116Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro (INFN LNLN), Legnaro, Italy 117 Istituto Nazionale di Fisica Nucleare Sezione di Bari (INFN BA), Bari, Italy 118 Istituto Nazionale di Fisica Nucleare, Sezione di Bologna (INFN BO), Bologna, Italy 119 Istituto Nazionale di Fisica Nucleare, Sezione di Cagliari (INFN CA), Cagliari, Italy 120 Istituto Nazionale di Fisica Nucleare, Sezione di Catania (INFN CT), Catania, Italy 121 Istituto Nazionale di Fisica Nucleare, Sezione di Cosenza (INFN CS), Cosenza, Italy 122 Istituto Nazionale di Fisica Nucleare, Sezione di Ferrara (INFN FE), Ferrara, Italy 123 Istituto Nazionale di Fisica Nucleare, Sezione di Firenze (INFN FI), Florence, Italy 124 Istituto Nazionale di Fisica Nucleare, Sezione di Genova (INFN GE), Genoa, Italy 125 Istituto Nazionale di Fisica Nucleare, Sezione di Lecce (INFN LE), Lecce, Italy 126Istituto Nazionale di Fisica Nucleare, Sezione di Milano Bicocca (INFN MIB), Milan, Italy 127 Istituto Nazionale di Fisica Nucleare, Sezione di Milano (INFN MI), Milan, Italy 128 Istituto Nazionale di Fisica Nucleare, Sezione di Napoli (INFN NA), Naples, Italy 129 Istituto Nazionale di Fisica Nucleare, Sezione di Padova (INFN PD), Padua, Italy 130 Istituto Nazionale di Fisica Nucleare, Sezione di Pavia (INFN PV), Pavia, Italy 131 Istituto Nazionale di Fisica Nucleare, Sezione di Perugia (INFN PG), Perugia, Italy 132Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Università di Pisa (INFN PI), Pisa, Italy 133 Istituto Nazionale di Fisica Nucleare, Sezione di Roma 1 (INFN Roma 1), Rome, Italy 134Istituto Nazionale di Fisica Nucleare, Sezione di Roma Tor Vergata (INFN Roma 2), Rome, Italy 135 Istituto Nazionale di Fisica Nucleare, Sezione di Roma Tre (INFN Roma 3), Rome, Italy 136 Istituto Nazionale di Fisica Nucleare, Sezione di Torino (INFN TO), Turin, Italy 137 Istituto Nazionale di Fisica Nucleare, Sezione di Trieste (INFN TS), Trieste, Italy 138 ITER (ITER), Cadarache, France 139 Ivane Javakhishvili T'bilisi State University (TSU), T'bilisi, Georgia 140 Izmir University of Economics (IUE), Izmir, Turkey 141 Johannes-Gutenberg-Universität (JGU), Mainz, Germany 142 John Adams Institute for Accelerator Science, The Chancellor, Masters and Scholars of the University of Oxford (JAI), Oxford, UK 143 Joint Institute for Nuclear Research (JINR), Dubna, Russia 144 Julius-Maximilians-Universität Würzburg (UWUERZBURG), Würzburg, Germany 145 Kahramanmaras Sutcu Imam University (KSU), Kahramanmaras, Turkey 146 Karlsruher Institut für Technologie (KIT), Karlsruhe, Germany 147 Katholieke Universiteit Leuven Research & Development (LRD), Louvain, Belgium 148 Key Laboratory of Theoretical Physics, Chinese Academy of Science (SKLTP ITP CAS), Beijing, P.R. China 149 King's College London (KCL), London, UK 150 Kyoto University (Kyodai), Kyoto, Japan 151 Kyungpook National University (KNU), Sankyuk-dong, Republic of Korea 152Laboratoire d'Annecy-Le-Vieux de Physique des Particules (CNRS/IN2P3/LAPP), Annecy, France 153 Laboratoire de l'Accélérateur Linéaire, Universitéde Paris Sud (CNRS/IN2P3/UPSUD/ LAL), Orsay, France 154 Laboratoire de Physique Nucléaire et de Hautes Energies (LPNHE), Paris, France -- 155Laboratoire de Physique Subatomique et de Cosmologie Grenoble (LPSC), Grenoble, France 156Laboratoire de Physique Théorique et Hautes Energies (CNRS/Sorbonne/LPTHE), Paris, France 157 Laboratoire Leprince-Ringuet, Ecole Polytechnique (LLR), Palaiseau, France 158 Laboratório de Instrumentac¸ão e Física Experimental de Partículas (LIP), Lisbon, Portugal 159 Latitude Durable (LD), Geneva, Switzerland 160 Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA, USA 161 Linde Kryotechnik AG (Linde), Pfungen, Switzerland 162 Loughborough University (LBoro), Loughborough, UK 163 Ludwig Maximilians University of Munich (LMU), Munich, Germany 164 Luvata Pori Oy (Luvata), Pori, Finland 165 MAN Energy Solutions Schweiz AG (MAN ES), Zürich, Switzerland 166 Marian Smoluchowski Institute of Physics, Jagiellonian University (UJ), Kraków, Poland 167 Massachusetts Institute of Technology (MIT), Cambridge, MA, USA 168 Max-Planck-Institut für Kernphysik (MPIK), Heidelberg, Germany 169 Max-Planck-Institut für Physik (MPP), Munich, Germany 170 Ministère de l'Europe et des Affaires étrangères (MEAE), Paris, France 171 Monash University (Monash), Melbourne, Australia 172 MTA Wigner Research Centre for Physics (Wigner), Budapest, Hungary 173 Mustafa Kemal Üniversitesi (MKU), Hatay, Turkey 174 Nankai University (NKU), Tianjin, P.R. China 175 Nationaal instituut voor subatomaire fysica (NIKHEF), Amsterdam, The Netherlands 176 National Centre for Scientific Research Demokritos (NCSRD), Athens, Greece 177National High Magnetic Field Laboratory, Florida State University (MagLab), Tallahassee, FL, USA 178 National Institute of Chemical Physics and Biophysics (NICPB), Tallin, Estonia 179 National Research Center Kurchatov Institute (NRCKI), Moscow, Russia 180 National Research Nuclear University MEPhI (MEPhI), Moscow, Russia 181 National Science Centre Kharkov Institute of Physics and Technology (KIPT), Kharkov, Ukraine 182 National Technical University of Athens (NTUA), Athens, Greece 183 Naturhistorisches Museum Wien (NHM), Vienna, Austria 184 Niels Bohr Institute, Copenhagen University (NBI), Copenhagen, Denmark 185 Nigde Ömer Halisdemir University (OHU), Nigde, Turkey 186 Northern Illinois University (NIU), DeKalb, IL, USA 187 Northwestern University (NU), Evanston, IL, USA 188 Novosibirsk State University (NSU), Novosibirsk, Russia 189 Otto-von-Guericke-Universityät Magdeburg (OVGU), Magdeburg, Germany 190 Oxford University (UOXF), Oxford, UK 191 Paul Scherrer Institute (PSI), Villigen, Switzerland 192 Peking University (PU), Beijing, P.R. China 193 Perimeter Institute for Theoretical Physics (PI), Watterloo, Canada 194Petersburg Nuclear Physics Institute, NRC "Kurchatov Institute" (PNPI), Gatchina, Russia 195 Piri Reis University (PRU), Istanbul, Turkey 196Pittsburgh Particle physics, Astrophysics & Cosmology Center and Department of Physics & Astronomy, University of Pittsburgh (PITT PACC), Pittsburgh, PA, USA 197 Princeton University (PU), Princeton, NJ, USA 198PRISMA Cluster of Excellence, Inst. für Physik, Johannes-Gutenberg-Universität (PRISMA), Mainz, Germany 199 Pusan National University (PNU), Busan, Republic of Korea 200 Queen's University (Queens U), Kingston, Canada 201 RAMENTOR Oy (RAMENTOR), Tampere, Finland 202 Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Aachen, Germany 203 Riga Technical University (RTU), Riga, Latvia 204 Royal Holloway University (RHUL), London, UK 205 Ruder Boskovic Institute (RBI), Zagreb, Croatia 206 Ruprecht Karls Universität Heidelberg (RKU), Heidelberg, Germany 207 Rutgers, The State University of New Jersey (RU), Piscataway, NJ, USA 208 Sapienza Università di Roma (UNIROMA1), Rome, Italy 209School of Particles and Accelerators, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran 210 School of Physics and Astronomy, University of Glasgow (SUPA), Glasgow, UK 211Science and Technology Facilities Council, Daresbury Laboratory (STFC DL), Warrington, UK 212Science and Technology Facilities Council, Appleton Laboratory (STFC RAL), Rutherford, Didcot, UK 213 scMetrology SARL (scMetrology), Geneva, Switzerland 214 Scuola Int. Superiore di Studi Avanzati di Trieste (SISSA), Trieste, Italy 215 Scuola Normale Superiore (SNS), Pisa, Italy 216 Seoul National University (SNU), Seoul, Republic of Korea 217 Sevaplan und Wurm Schweiz AG (WURM), Winterthur, Switzerland 218 Shahid Beheshti University (SBUT), Tehran, Iran 219 Shanghai Jiao Tong University (SJTU), Shanghai, P.R. China 220 Shirokuma GmbH (Shirokuma), Wetzikon, Switzerland 221Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University (SINP MSU), Moscow, Russia 222 Southern Federal University (SFU), Rostov-on-Don, Russia 223 Southern Methodist University (SMU), Dallas, TX, USA 224Sri Guru Tegh Bahadur Khalsa College, University of Delhi (SGTB Khalsa College), New Delhi, India 225 Stanford National Accelerator Center (SLAC), Menlo Park, CA, USA 226 Stanford University (SU), Stanford, CA, USA 227 Stony Brook University (SBU), Stony Brook, NY, USA 228 Technische Universität Darmstadt (TU Darmstadt), Darmstadt, Germany 229 Technische Universität Dortmund (TU Dortmund), Dortmund, Germany 230 Technische Universität Dresden (TU Dresden), Dresden, Germany 231 Technische Universität Graz (TU Graz), Graz, Austria 232 Technische Universität Wien (TU Wien), Vienna, Austria 233 Tel Aviv University (TAU), Tel Aviv, Israel 234 The Citadel, The Military College of South Carolina (Citadel), Charleston, SC, USA 235 The Pennsylvania State University (PSU), University Park, PA, USA 236 The University of Tokyo (Todai), Tokyo, Japan 237 Thomas Jefferson National Accelerator Facility (JLab), Newport News, VA, USA 238 TOBB University of Economics and Technology (TOBB ETU), Ankara, Turkey 239 Tokyo Institute of Technology (Tokyo Tech), Tokyo, Japan 240 Trinity College Dublin (TCD), Dublin, Ireland 241 Tri-University Meson Facility (TRIUMF), Vancouver, Canada 242 Tsinghua University (THU), Beijing, P.R. China 243 Tsung-Dao Lee Institute (TDLI), Shanghai, P.R. China 244 Uludag University (ULUÜ), Bursa, Turkey 245 Universidad Autónoma de Sinaloa (UAS), Culiacán, Mexico 246 Universidad de Guanajuato (UGTO), Guanajuato, Mexico 247 Universidad de La Laguna (ULL), La Laguna, Spain 248 Universidad de la República (Udelar), Montevideo, Uruguay 249 Universidad de los Andes (Uniandes), Bogotá, Colombia 250 Universidade de São Paulo (USP), São Paulo, Brazil 251 Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil -- 252 Universidade Federal de Pelotas (UFPel), Pelotas, Brazil 253 Universidade Federal de Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil 254Università degli Studi Roma Tre – Centro Ricerche Economiche e Sociali Manlio Rossi-Doria (EDIRC), Rome, Italy 255 Università della Calabria (UNICAL), Arcavacata, Italy 256 Università del Salento (UNISALENTO), Lecce, Italy 257 Università di Bari (UNIBA), Bari, Italy 258 Università di Bologna (UNIBO), Bologna, Italy 259 Università di Cagliari (UNICA), Cagliari, Italy 260 Università di Catania (UNICT), Catania, Italy 261 Università di Ferrara (UNIFE), Ferrara, Italy 262 Università di Firenze (UNIFI), Florence, Italy 263 Università di Genova (UNIGE), Genoa, Italy 264 Università di Insubria (UNINSUBRIA), Milan, Italy 265 Università di Lecce(UNILE), Lecce, Italy 266 Università di Milano (UNIMI), Milan, Italy 267 Università di Padova (UNIPD), Padua, Italy 268 Università di Parma (UNIPR), Parma, Italy 269 Università di Pavia (UNIPV), Pavia, Italy 270 Università di Perugia (UNIPG), Perugia, Italy 271 Università di Roma Sapienza (UNIROMA1), Rome, Italy 272 Università di Roma Tor Vergata (UNIROMA2), Rome, Italy 273 Università di Roma Tre (UNIROMA3), Rome, Italy 274 Università di Torino (UNITO), Turin, Italy 275 Università di Udine (UNIUD), Udine, Italy 276 Universität Hamburg (UHH), Hamburg, Germany 277 Universität Heidelberg (HEI), Heidelberg, Germany 278 Universitat Politecnica de Catalunya (UPC), Barcelona, Spain 279 Universität Siegen (U Siegen), Siegen, Germany 280 Universität Tübingen (TU), Tübingen, Germany 281 UniversitéClermont Auvergne (UCA), Aubière, France 282 UniversitéGrenoble Alpes (UGA), Grenoble, France 283 University College London (UCL), London, UK 284 University of Applied Sciences Technikum Wien (UAS TW), Vienna, Austria 285 University of Arizona (UA), Tucson, AZ, USA 286 University of Basel(UNIBAS), Basel, Switzerland 287 University of Belgrade (UB), Belgrade, Serbia 288 University of Bergen (UiB), Bergen, Norway 289 University of Bern (UNIBE), Bern, Switzerland 290 University of Birmingham (UBIRM), Birmingham, UK 291 University of Bristol (UOB), Bristol, UK 292 University of California Berkeley (UCB), Berkeley, CA, USA 293 Davis (UCD), University of California, Davis, CA, USA 294 Irvine (UCI), University of California, Irvine, CA, USA 295 San Diego (UCSD), University of California, San Diego, CA, USA 296 University of California Santa Barbara (UCSB), Santa Barbara, CA, USA 297 University of California Santa Cruz (UCSC), Santa Cruz, CA, USA 298 University of Cambridge (CAM), Cambridge, UK 299 University of Chicago (UCHI), Chicago, IL, USA 300 University of Cincinnati (UC), Cincinnati, OH, USA 301 University of Edinburgh (ED), Edinburgh, UK 302 University of Florida (UF), Gainesville, FL, USA 303 University of Geneva (UniGE), Geneva, Switzerland 304 University of Illinois at Urbana Champaign (UIUC), Urbana Champaign, IL, USA 305 University of Iowa (UIowa), Iowa City, IA, USA -- The Auvergne-Rhône-Alpes regional government is headed by a prefect who is supported by an office (Secrétariat Général de la Région Auvergne-Rhône-Alpes, SGAR) located in Lyon. Within this administration, the prefect is the representative of the French Republic. The SGAR and the prefect's office work together on all development activities in the area. In 2016 the SGAR launched an analysis so that the prefect, and in turn the French national administration, could be informed about a significant extension of CERN's infrastructure and to estimate the associated administrative and financial impacts for France. This activity led to the establishment of a series of regular meetings with CERN for the development of the preparatory phase. France promotes a "participative democracy" [549–551], calling for a process to find a consensus through open discussions amongst all stakeholders in the project from the conceptual stage onwards. The process starts with the development of the basic concept, a feasibility study concerning the infrastructural challenges, a proposal for the governance and funding and a socio-economic cost-benefit analysis. The infrastructural changes concern a wide range of topics: the use of excavation material, a concept for managing conventional waste during all project phases, an energy management plan that can be integrated with the territorial energy balance plan, plans for the consumption of resources such as water, proposals for synergies with the host state to contribute to the territorial development, the development of traffic and mobility concepts and further topics. CEREMA6, a public entity associated with the ministry of ecological transition and solidarity and the ministry of territorial cohesion, has produced a report for the SGAR and the prefect on the impact of an FCC for the host state concerning administrative processes and the associated financial engagements [552]. -- MVDC distribution systems are an active area of academic research that spans various sectors including electrical engineering, electronics, information and computing technologies, reliability engineering, functional safety, economics and business analysis. Consequently, this is an ideal application to bring academic partners with complementary competencies from different geographical regions together at CERN in a concrete technological research project with tangible impact potential at academic levels, with high-educational value and with opportunities to work in a close-to-market environment. Specifically, EPFL (Lausanne, Switzerland), a technical university, has an active programme on the development of MVDC power distribution networks with support from the Swiss Federal Office of Energy (SFOE). -- The research, which led to this publication has received funding from the European Union's Horizon 2020 research and innovation programme under the grant numbers 654305 (EuroCirCol), 764879 (EASITrain), 730871 (ARIES), 777563 (RI-Paths) and from FP7 under grant number 312453 (EuCARD-2). The information herein only reflects the views of its authors. The European Commission is not responsible for any use that may be made of the information. Trademark notice: All trademarks appearing in this report are acknowledged as such. -- Emittance The area in phase space occupied by a particle beam. The units are mm-milliradians for transverse emittance and eV·s for longitudinal emittance. EN European norms are documents that have been ratified by one of the three ESOs (European Standardisation Organisations), CEN, CENELEC or ETSI; recognised as competent in the area of voluntary technical standardisation as for the EU Regulation 1025/2012. EOT The most common type of overhead crane, found in many factories. These cranes are electrically operated by a control or remote control pendant, or from an operator cabin attached to the crane. EPFL The École polytechnique fédérale de Lausanne is one of the two Swiss Federal Institutes of Technology. EPPSU European Particle Physics Strategy Update. See also https:// europeanstrategy.cern. ERL Energy recovery Linac. ERMC Enhanced racetrack model coil. ES Electro static. ESD Electron-stimulated desorption. ESFRI European strategy forum for research infrastructures. Espoo Convention The Espoo Convention sets out the obligations of parties to assess the environmental impact of certain activities at an early stage of planning. It also lays down the general obligation of states to notify and consult each other on all major projects under consideration that are likely to have a significant adverse environmental impact across boundaries. ESPP European Strategy for Particle Physics. See also https:// europeanstrategy.cern. ESRF The European Synchrotron Radiation Facility is a joint research facility sit-uated in Grenoble, France, and supported by 22 countries (13 member coun-tries: France, Germany, Italy, UK, Spain, Switzerland, Belgium, The Netherlands, Denmark, Finland, Norway, Sweden, Russia and 9 associate countries: Austria, Portugal, Israel, Poland, Czech Republic, Hungary, Slovakia, India and South Africa). ESS Energy storage system. ETHZ The Eidgenössische Technische Hochschule Zürich is one of the two Swiss Federal Institutes of Technology. EU European Union. EuCARD2 A FP7 EC funded research and development project in the area of particle accelerator technologies. EuroCirCol A H2020 EC funded research and development project to develop the foundations of a future circular hadron collider. EW Electroweak. EWPO Electroweak precision observables. EWPT Electroweak phase transition. EWSB Electroweak symmetry breaking. EXP Experiment. Experiment insertion region Place in the particle collider hosting the interac-tion region in which the two beams are brought to collision and the surrounding particle physics experiments. EXT Extraction.

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With NATO's 75th anniversary summit drawing near, German Chancellor Olaf Scholz told the Munich Security Conference in February that Germany would this year meet NATO's 2% of GDP target for defense spending and would sustain this level "through the 2020s and 2030s."But Bastian Giegerich, the head of the London-based International Institute for Security Studies, has said that reversing the effects across Europe of more than 20 years of underfunding of defense capabilities will take at least a decade of substantially increased defense spending. He's not alone in thinking this way, and for good reason. Germany's 2024 budget allocates 51.8 billion euros for defense, by itself short of the 2% of GDP NATO benchmark. Germany seems on course, however, to meet the target by drawing down the 100 billion euro emergency fund announced by Scholz in his famous Zeitenwende (epochal change) speech to the Bundestag in February 2022. Disbursements from this fund are projected to keep Germany's defense spending at or above the 2% of GDP mark through 2028, after which Germany plans to fund defense through the regular budget process. Achieving this will require an increase of approximately 30 billion euros over the 2024 defense outlay. An increase of this magnitude to defense spending from the regular budget process will require overcoming very serious obstacles. Germany has well established limits on the fiscal deficit, which will create politically destabilizing distributional conflict when other spending priorities are forced to adjust to make room for a bigger defense budget.. This constraint will be even more binding if the economy, expected to grow at only 0.2% this year, remains weak. Fiscal probity is baked into German political culture and shored up by formal legal constraints. The "debt brake" written into the constitution in 2009 holds the federal budget deficit to 0.35% in any budget year. The opposition Christian Democratic (CDU/CSU) party, which, according to current polling trends, seems likely to return to power in the 2025 elections, is wary of any attempt to circumvent or reform the debt brake, which legally can be suspended only by invoking "emergency" conditions, as was done to fund pandemic spending, and to unlock 100 billion euros for defense spending in 2022. Last November, Germany's Constitutional Court ruled against the government's plan to repurpose 60 billion euros of unspent COVID funding to pay for green energy transition programs. The ruling coalition had to scramble to fill the hole in its budget, exposing the vulnerability of Germany's fiscal policy to distributional constraints. Farmers took protests onto the streets of Berlin to demand restoration of their diesel fuel subsidy. This kind of social tension is likely to follow any attempt to shift massive resources to the defense sector by cutting other programs. The green energy transition remains a priority for the coalition's two main parties — the Social Democrats (SPD) and the Greens — even though both are fully convinced of the need to boost defense spending. The fiscally conservative Free Democrats (FDP) and their leader, Finance Minister Christian Lindner, adamantly oppose reforming the debt brake or raising taxes. The only obvious way to square this circle would be to consider the continuing war in Ukraine an emergency and thereby unlock another 100 billion euros. This is obviously not an ideal way to finance a program of rearmament that might take decades, and such a maneuver might not survive scrutiny by the Constitutional Court in any case. It is becoming evident that, even with the provision of emergency funding, the defense industrial base can expand only gradually, and weapons procurement processes are limited by the time needed to manufacture new weapons and equipment, whether from Germany, elsewhere in Europe or the United States. For example, the 18 Leopard 2 battle tanks ordered to replace those supplied to Ukraine will arrive two years from now at the earliest. Meanwhile, Ukrainian president Zelensky recently assailed Germany for not delivering the Taurus missiles; he claimed Berlin decided the missiles were necessary for defending Germany instead.Social Constraints: Leadership and Public AttitudesThe German military was underfunded for years before February 2022, because the political leadership absorbed the liberal triumphalism of the 1989 democratic revolutions in Central and Eastern Europe and believed history pointed to global convergence on the liberal democratic model.Efforts to expand military recruitment began after the 2014 Russian takeover of Crimea, but has failed to attract new recruits in sufficient numbers. The number of troops remains stuck at 180,000. Some are now calling for reinstituting mandatory military service.The most effective and vocal advocate for Germany's rearmament is Defense Minister Boris Pistorius, an SDP politician widely touted as a possible successor to Scholz. Pistorius has said that the Bundeswehr must be made "kriegstüchtig" (war ready) and warned that Russia might attack a NATO member within the coming 8-10 years.These statements, very much against the grain of Germany's antecedent anti-militarist political culture, have not dented Pistorius' popularity. German elites and, to a lesser extent, the broader society seem to be moving toward greater acceptance of the need for national rearmament.The European Vision: Too Many Cooks?The European Commission has advanced its own plans to coordinate the financing of rearmament across Europe, favoring and fostering synergies among European defense-industrial firms. In principle, this initiative should pose no problem for Germany since Scholz, a committed European, has repeatedly stated that the EU is the framework for Germany foreign and security policy.Nevertheless, the Commission risks competing with member nations for available resources for equipment and weapons acquisition. Most member countries, including Germany and France, conceive of defense cooperation in a multilateral pan-European context, but would insist that member nations remain in the driver's seat.Emmanuel Macron's exhaustive vision for Europe— the "Sorbonne II" speech of April 26 — dealt extensively with the European imperative to develop a more capable conventional deterrent, albeit within NATO.His framing of the issue was the stark warning that "Our Europe can die," but he did not endorse any pooling of national sovereignty on defense policy. On the contrary, he pledged personally to convene "all partners" to develop a "new defense paradigm" for the "credible defense of the European continent."This is an intergovernmental framework rather than one featuring a leading role for the European Commission.Why the Path Ahead is DifficultBastian Giegerich of IISS says that for Germany "the mental shift, the societal resilience" needed to underpin rearmament "has not happened." This is true, but it is not only a matter of changing hearts and minds. Germany's limitations are embodied in its institutional framework and very resistant to change, given the perceived challenges from the populist right, the climate policy imperative, its generous social safety net, the fragmented party system, the self-imposed but broadly popular fiscal constraints, and complex coordination problems with key partners (above all France) and the European Commission. This transformation, even if embraced without reservation by Scholz or his successors, is a vastly complex and fraught agenda.

The RAND corporation's Samuel Charap and Johns Hopkins University professor Sergey Radchenko published a detailed timeline and analysis of the talks between Russian and Ukrainian negotiators just after the Russian invasion in February 2022 that could have brought the war to an end just weeks after it had begun.
Much of the piece confirms or elucidates parts of the narrative that had previously been reported. In the spring of 2022, the two sides appeared relatively close to a deal, one that, according to the authors, would "have ended the war and provided Ukraine with multilateral security guarantees, paving the way to its permanent neutrality and, down the road, its membership in the EU."
But due to a combination of changing battlefield dynamics that convinced Ukrainian President Volodymyr Zelensky that he could win the war militarily, Western allies' hesitance to engage diplomatically with Russia and simultaneous ramping up of military support for Ukraine, and the discovery that Russian forces had committed atrocities in Bucha, the talks eventually fell apart.
On some of these points, the authors contend that earlier accounts have been overstated. The idea that the U.S. and the UK "forced" Zelensky to back out of peace talks is "baseless," say Charap and Radchenko, though they acknowledge that "the lack of Western enthusiasm does seem to have dampened his interest in diplomacy."
On the suggestion that the discovery of war crimes convinced the Ukrainian president to abandon negotiations, the authors note discussions "continued and even intensified in the days and weeks after the discovery of Russia's war crimes, suggesting that the atrocities at Bucha and Irpin were a secondary factor in Kyiv's decision-making."
But taken together, these factors, along with certain details of the agreement that were never finalized, were enough to imperil the negotiations.
In the two years since Ukrainian and Russian interlocutors last convened, the realities on the ground have changed. By April 2022, Vladimir Putin had likely realized that he would fail to achieve his most maximalist war aims. Now, with Western aid stalled and the war tilting in Moscow's favor, Ukraine is in a less favorable negotiating position than it was and Russia may be less inclined to enter talks.
But, as George Beebe and Anatol Lieven detail in a recent Quincy Institute paper, all sides still have a reason to pursue a diplomatic solution, one that could both end the war and provide for a new European security architecture once the fighting ceases.
As Charap and Radchenko note in their Foreign Affairs piece, one of the reasons the original talks broke down was because the two sides were more focused on the broader endgame rather than on shorter-term solutions.
"A final reason the talks failed is that the negotiators put the cart of a postwar security order before the horse of ending the war," they write. "The two sides skipped over essential matters of conflict management and mitigation (the creation of humanitarian corridors, a cease-fire, troop withdrawals) and instead tried to craft something like a long-term peace treaty that would resolve security disputes that had been the source of geopolitical tensions for decades."
The two years of war have only increased distrust between Russia, Ukraine, and Kyiv's Western backers, and diplomacy appears to be more difficult today than it was in 2022. But, say Charap and Radchenko, Zelensky and Putin surprised us once before with the concessions they may have been willing to make, and perhaps they will do so again. The consequences of that failed first effort at diplomacy are clear, as Thomas Graham, former senior director for Russia on the National Security Council staff, argued this week.
"The great tragedy of the Russian-Ukrainian war is that it will ultimately prove to have been futile. The likely outcome — territorial adjustments in Moscow's favor, security guarantees for Ukraine and Russia — could have been peaceably negotiated beforehand had leaders had a firmer grasp of the real balance of power or greater political courage," he wrote in the Hill. "The cost of failed diplomacy is already hundreds of thousands of lives lost and hundreds of billions of dollars' worth of property destroyed."
In other diplomatic news related to the war in Ukraine:
— After months of waiting, the House may hold a vote to give Ukraine another tranche of aid over the weekend. On Wednesday, Speaker Mike Johnson (R-La.) introduced four separate bills, including one that will provide approximately $60 billion in aid for Kyiv. The House Speaker is already facing backlash from members of his own party, but the legislation is likely to have enough bipartisan support to pass if it is brought to the floor for a vote.
— There are reportedly increasing points of tension between Washington and Kyiv as Ukraine awaits more aid and its war effort falters. Zelensky was frustrated that Washington has not offered his country the same missile defense help as it provided to Israel during Iran's strikes over the weekend. "European skies could have received the same level of protection long ago if Ukraine had received similar full support from its partners in intercepting drones and missiles," Zelensky wrote in a post on X. "Terror must be defeated completely and everywhere, not more in some places and less in others."
Moreover, Kyiv has expressed frustration over Washington's recommendations that Ukraine not strike Russian oil refineries, according to The Washington Post. Vice President Kamala Harris reportedly privately made the suggestion to Zelensky in February at the Munich Security Conference.
"The request, according to officials familiar with the matter, irritated Zelensky and his top aides, who view Kyiv's string of drone strikes on Russian energy facilities as a rare bright spot in a grinding war with a bigger and better-equipped foe. Zelensky brushed off the recommendation, uncertain whether it reflected the consensus position of the Biden administration, these people said." according to the Post. "Instead of acquiescing to the U.S. requests, however, Ukraine doubled down on the strategy, striking a range of Russian facilities, including an April 2 attack on Russia's third-largest refinery 800 miles from the front."
— Russia and Ukraine nearly struck a deal late last month to renew the agreement that allowed for the safety of shipping in the Black Sea before Kyiv suddenly pulled out, according to Reuters.
"A deal was reached in March 'to ensure the safety of merchant shipping in the Black Sea', and though Ukraine did not want to sign it formally, Kyiv gave its assent for Turkish President Tayyip Erdogan to announce it on March 30, the day before critical regional elections, the sources said," reports Reuters. The reason for Kyiv's withdrawal is unclear. Russia and Ukraine previously struck a deal to allow for safe shipping in June 2022 but Moscow withdrew from that agreement after one year.
U.S. State Department News
In a press briefing on Wednesday, State Department spokesman Vedant Patel urged the House to pass the aid bill for Ukraine quickly.
"So it certainly would not be hyperbole to say that every day matters, and the House, we believe, needs to act this week to support Ukraine and Israel as they respectively defend against Putin and the Russian Federation and the Iranian regime. And so this is something that we need Congress to provide urgently," Patel said.

In a recent interview, Pope Francis took stock of the war in Ukraine. "The strongest one is the one who looks at the situation, thinks about the people and has the courage of the white flag, and negotiates," the pope told Swiss media. The comment led to derision from Ukraine and its Western supporters, who saw in the pontiff's message a call to capitulate. (We'll leave aside the fact that, behind closed doors, some European diplomats are reportedly warming to the idea of a negotiated end to the war.)Pope Francis offered an easy target for criticism by referring to a white flag, the traditional symbol of surrender. But one of his key messages actually was, "Don't be ashamed to negotiate before things get worse." Pope Francis has often referred to the Ukrainian people as martyrs in this war; suggestions that his words are a gift to Putin are misguided and confuse his anti-war instincts for support of Russia's war effort.Pope Francis noted that "the word negotiate is a courageous word." Pierre Hazan, a senior adviser with the Centre for Humanitarian Dialogue and author of a new book on conflict mediation, would probably agree. Hazan cut his teeth as a journalist covering the Bosnia War and other conflicts before putting down the pen to take an active role in armed conflict negotiations. One of these was the peace process in the Basque Country that led the terrorist group Euskadi Ta Askatasuna (ETA) to lay down its arms. In "Negotiating with the Devil: Inside the World of Armed Conflict Mediation," the Swiss mediator mounts a strong defense of the importance of negotiation in the middle of a conflict.Before extolling the virtues of talks, Hazan acknowledges the potential pitfalls. Among other things, negotiations risk being manipulated by one of the parties. The author provides the example of the Munich Conference in 1938, which became the antechamber of Adolf Hitler's march on the European continent. There is also the possibility that talks become a smokescreen for violence. Hazan mentions here the Norwegian-led mediation between the Sri Lanka government and the Liberation Tigers of Tamil Eelam (LTTE), a group of ruthless insurgents fighting for a Tamil state. When the Sri Lankan government wiped out the LTTE in a final offensive in 2009, it also killed around 40,000 civilians in the process. On rare occasions, the problem is not that negotiations end up facilitating carnage but that there is simply no partner willing to talk. That is the case of ISIS or the extinct Shining Path in Peru, explains the Swiss mediator.These difficulties notwithstanding, for Hazan, the key question remains whether "negotiating with war criminals—including the worst of them—might save lives." To this, he replies that "with very few exceptions, the answer is yes, of course." Those who mediate in armed conflicts are forced to consider possibilities that are far removed from ideals of justice in the search for the least bad option, argues Hazan. This became more complicated after the 9/11 attacks, when President Bush declared a "War on Terror," and the room for negotiations with warring states, rebel groups, or terrorist organizations narrowed down dramatically. In this new context, remarks Hazan, "mediation, previously lauded, was pushed aside in favour of military solutions."If total victory over terrorists and rogue states was, as Bush suggested, both just and within reach, then there was little need for negotiation in this new world. If the goal was to export democracy and eliminate terrorism once and for all, Bush failed spectacularly on both accounts. By then, however, the world had already been defined in good-versus-evil terms. Thus, to conduct badly needed talks with the evil side of this simplistic equation (be it Iran, North Korea, or the Taliban) would have been seen as treason to our highest ideals. The U.S., with European countries often following suit, promoted a new paradigm according to which mediation was "perceived as an admission of weakness," writes Hazan.These dynamics can be observed in the case of former United Nations diplomat Álvaro de Soto, who resigned his position as envoy for the Middle East Peace Process in May 2007. After Hamas won the 2006 Palestinian elections, the international community halted direct funding to the Palestinian Authority. The rationale was that this would apply pressure on Hamas to recognize the state of Israel and renounce violence. The consequence was not a moderation in Hamas' positions but a steep increase in poverty among Palestinians and a deterioration of public services.De Soto opposed the aid blockade on Palestinians but had little room to maneuver, as the Peruvian diplomat himself explained in a secret report written before handing in his resignation. In the (subsequently leaked) report, de Soto argued U.S. pressure had "pummelled into submission" the U.N.'s role as a neutral mediator in the Middle East. As Hazan explains, one of the biggest obstacles for de Soto was that his superiors forbade him to continue talks with Hamas or the Syrian government.Hazan added a preface to the original French edition of his book to cover the events that followed Hamas' attack against Israel on October 7, when the militant group killed 1,200 people and took 240 hostages. Since then, Israel's military operation in the Gaza Strip has resulted in the death of at least 31,000 people. Hazan reflects on the Qatar-mediated ceasefire in Gaza that lasted for a week at the end of November 2023. The ceasefire, the author argues, was a historical development for at least two reasons. First, it was probably an unprecedented agreement, as hostages were directly exchanged for ceasefire days. And second, Qatar's role exemplified "the end of Western hegemony over the international system."Whether Western hegemony will be followed by something better is up for debate. However, when Hazan points to Turkey's role in the mediation of the grain deal between Russia and Ukraine, or to China's diplomatic efforts leading to the resumption of ties between Iran and Saudi Arabia, it is easy to recognize a pattern towards a broader plurality in the mediation scene.Hazan offered an interview last month discussing the latest developments in the Ukraine war, which are not included in the book. Hazan explained that he sees two main scenarios for a mediated solution in Ukraine. In the first one, a precarious calm would prevail and there would be a limited ceasefire with Russia and Ukraine technically at war for the foreseeable future. In the second one, what he calls the "Korean model," there would be a demilitarized zone between the two sides with Ukraine obtaining security guarantees and NATO/European Union membership. A more robust mediation process and peace agreement will only happen "if the military or the political situation changes radically either way," he argued.Based on his long-time experience, Hazan notes that "peace is a messy, chaotic business, as is the road that leads to it." There is no sense in negotiating only for negotiations' sake, and mediation is fraught with dangers.Yet experts should not be swayed by the supposed moral certitude of refusing to come to the table. Outright negation of the possibility of talks carries the risk of missing opportunities to settle for the lesser evil even as the greater good fades into the distance.

The text analyses the intelligence activity against Poland in the period 1944-1989. The paper also contains a case study, i.e. an analysis of the American intelligence service activity held against Poland. While examining the research thesis, the author used the documents and analyses prepared by the Ministry of Internal Affairs. In order to best illustrate the point, the author presented a number of cases of persons who spied for the USA, which was possible thanks to the analysis of the training materials of the Ministry of Internal Affairs directed to the officers of the Security Service and the Citizens' Militia. The text tackles the following issues: (1) to what extent did the character of the socio-political system influence the number of persons convicted for espionage against Poland in the period under examination?, (2) what was the level of interest of the foreign intelligence services in Poland before the year 1990?, (3) is it possible to indicate the specificity of the U.S. intelligence activity against Poland? 1) The analysis of data indicates that the period 1946-1956 witnessed a great number of convictions for espionage, which is often associated with the peculiar political situation in Poland of that time. Up to 1953, the countries of the Eastern bloc had reproduced the Stalin's system, which only ceased due to the death of Stalin himself. Since then, the communist systems gradually transformed into the system of nomenklatura. Irrespective of these changes, Poland still witnessed a wave of repressions, which resulted from the threats continuously looming over the communist authorities – combating the anti-communist underground movement, fighting with the Ukrainian Insurgent Army, the Polish government-in-exile, possible revisionism of borders, social discontent related to the socio-political reforms. Hence, a great number of convictions for espionage at that time could be ascribed to purely political sentences. Moreover, equally significant was the fact that the then judicial practice was preoccupied assessing negatively any contacts and relations with foreigners. This excessive number of convictions could ensue from other criminal-law provisions, which applied with respect to the crimes against the State, including espionage. What is also important is the fact that in the Stalin's period the judiciary personnel acquired their skills and qualifications through intensive courses in law with the predominant spirit of the theory of evidence and law by Andrey Vyshinsky. Additionally, by the decree of 1944 the Penal Code of the Polish Armed Forces was introduced; the code envisaged the increase in the number of offences classified as penalised with death penalty, whereas the high treason was subject to the military jurisdiction (the civilians were prosecuted in military courts till 1955; the espionage, however, still stood under the military jurisdiction). In 1946, there was introduced the Decree on particularly dangerous crimes in the period of the State's recovery, which was later called a Small Penal Code. 2) The interest that foreign intelligence services expressed in relation to Poland was similar to the one they had in all countries of Eastern and Central Europe. In the case of Poland, it should be noted that foreign intelligence services recruited Polish citizens who had previously stayed abroad and after WWII returned to their home country. The services also gathered information from Poles staying in immigrant camps (e.g. in FRG). The activity of the American intelligence service on the territory of FRG and West Berlin played a key role. The documents of the Ministry of Internal Affairs pointed to the global range of this activity, e.g. through the recruitment of Polish sailors in the ports of the Netherlands, Japan, etc. In line with the development in the 1970s, espionage, which had so far concentrated on the defence and strategic sectors, became focused on science and technology of the People's Republic of Poland. The acquisition of collaborators in academic circles was much easier, as PRL opened to academic exchange. Due to the system of visas, the process of candidate selection for intelligence services (e.g. the American) began in embassies. In the 1980s, the activity of the foreign intelligence services concentrated on the specific political situation in Poland, i.e. the growing significance of the "Solidarity" social movement. 3) The specificity of the American intelligence activity against Poland was related to the composition of the residency staff, which was the largest in comparison to other Western countries. The wide range of these activities can be proved by the quantitative data of convictions for espionage in the years 1944-1984 (however, one has to bear in mind the factors mentioned earlier in the text, which led to the misinterpretation of these data). Analysing the data and the documents prepared by the Ministry of Internal Affairs, one should treat them with caution, as, frequently, the Polish counter-intelligence service used to classify the ordinary diplomatic practice and any contacts with foreigners as espionage threats. It is clearly visible in the language of the training materials concerned with "secret service methods of the intelligence activity" as well as in the documents on operational activities of the Security Service in relation to foreigners. The level of interest the USA had in Poland was mirrored in the classification of diplomatic posts, according to which Warsaw occupied the second place (the so-called Group "B") on the three-point scale. The CIA experienced spectacular defeats during their activity in Poland: supporting the Polish underground anti-communist organisation Freedom and Independence and the so-called Munich-Berg episode (both cases took place in the 1950s). The text focuses only on selected issues related to the espionage activities against Poland. Similarly, the analysis of the problem has been based on selected sources, which has limited the research scope - however, it was not the aim of the author to present the espionage activity against Poland in a comprehensive way. In order to assess the real threat posed by the espionage activity, one should analyse the case of persons convicted for espionage in the period 1944-1989, as the available quantitative data, mentioned in the text, cannot constitute an explicit benchmark for the scale of espionage activity. The inaccuracies in the interpretation of data and variables, which can affect the evaluation of this phenomenon, have been pointed out in the text. ; The text is treats of the espionage against Poland in the period 1944-1989. The above analysis has been supplemented with the quantitative data from the period 1944-1984 as regards those convicted for participating in, acting for, and passing on information to the foreign intelligence agencies. The espionage issues were presented on the example of the American intelligence activity, which was illustrated by the cases of persons who were convicted for espionage. While examining the research thesis, the author used the documents and analyses prepared by the Ministry of Internal Affairs, which were in its major part addressed to the Security Service and the Citizens' Militia officers. The author made an attempt at the verification of the following research hypotheses: (1) to what extent did the character of the socio-political system influence the number of persons convicted for espionage against Poland in the period under examination (1944-1989)?, (2) what was the level of foreign intelligence services' interest in Poland before the year 1990?, (3) is it possible to indicate the specificity of the U.S. intelligence activity against Poland?