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6 pags., 4 figs., 1 tab. -- Open Access funded by Creative Commons Atribution Licence 4.0 ; The first 2(+) and 3(-) states of the doubly magic nucleus Sn-132 are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The Sn-132 ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a Pb-206 target. Deexciting gamma rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0(g.s)(+) -> 2(1)(+), 0(g.s)(+) -> 3(1)(-), and 2(1)(+) -> 3(1)(-) in Sn-132. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2; 0(g.s)(+) -> 2(1)(+)) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of Sn-132. ; The research leading to these results has received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 654002. This work was supported by the German BMBF under Contract No. 05P15PKCIA and Verbundprojekt No. 05P2015, in part by the High Performance Computing Infrastructure Strategic Program (Grant No. hp150224), in part by MEXT and Joint Institute for Computational Fundamental Science and a priority issue (elucidation of the fundamental laws and evolution of the universe) to be tackled by using the Post "K" Computer (Grants No. hp160211 and No. hp170230), in part by the HPCI system research project (Grant No. hp170182), by the CNS-RIKEN joint project for large-scale nuclear-structure calculations, in part by the Spanish Ministry of Economy, Industry and Competitiveness through Project No. FPA2017-87568-P, by FWO-Vlaanderen (Belgium), by GOA/2010/010 (BOF KU Leuven), and by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12). A. V. and L. K. thank the Bonn-Cologne Graduate School of Physics and Astronomy for financial support. J. P. and D. M. C. acknowledge the Academy of Finland (Contract No. 265023). G. R. acknowledges support by Bulgarian National Science Fund under Grant No. DN08/23/16. L. P. G. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska- Curie Grant Agreement No. 665779. ; Peer Reviewed

5 pags., 6 figs. ; Single-neutron states in the , isotope 79Zn have been populated using the 78Zn(d, p)79Zn transfer reaction at REX-ISOLDE, CERN. The experimental setup allowed the combined detection of protons ejected in the reaction, and of γ rays emitted by 79Zn. The analysis reveals that the lowest excited states populated in the reaction lie at approximately 1 MeV of excitation, and involve neutron orbits above the shell gap. From the analysis of γ-ray data and of proton angular distributions, characteristic of the amount of angular momentum transferred, a configuration was assigned to a state at 983 keV. Comparison with large-scale-shell-model calculations supports a robust neutron shell-closure for 78Ni. These data constitute an important step towards the understanding of the magicity of 78Ni and of the structure of nuclei in the region. ; This work was supported by the European Commission through the Marie Curie Actions Contracts Nos. PIEFGA-2011-30096 (R.O.) and PIEFGA-2008-219175 (J.P.), by the Spanish Ministerio de Ciencia e Innovación under contracts FPA2009-13377-C02 and FPA2011-29854-C04, by the Spanish MEC Consolider – Ingenio 2010, Project No. CDS2007-00042 (CPAN), by FWO-Vlaanderen (Belgium), by GOA/2010/010 (BOF KU Leuven), by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12), by the European Union Seventh Framework Programme through ENSAR, contract no. RII3-CT-2010-262010, and by the German BMBF under contracts 05P09PKCI5, 05P12PKFNE, 05P12RDCIA and 06DA9036I. R.O., R.C., J.F.W.L., V.L. and J.F.S. also acknowledge support from STFC, Grant Nos. PP/F000944/1, ST/F007590/1, and ST/J000183/2.

Background Currently, no validated clinical endpoints for treatment studies exist for intermediate age-related macular degeneration (iAMD). Objective The European MACUSTAR study aims to develop and clinically validate adequate clinical endpoints for future treatment studies in iAMD and to identify early determinants of disease progression to late stage AMD. Material and methods The MACUSTAR study protocol was developed by an international consortium of researchers from academia, the pharmaceutical industry and medical device companies. The MACUSTAR project is funded by the Innovative Medicines Initiative 2 (IMI2) of the European Union. Results The MACUSTAR study consists of a cross-sectional and a longitudinal investigation. A total of 750 subjects with early, intermediate and late AMD as well as control subjects with no signs of AMD will be included with a follow-up period of 3 years. Overall, 20 European study centers are involved. Conclusion The MACUSTAR project will generate large high-quality datasets, which will allow clinical validation of novel endpoints for future interventional trials in iAMD. The aim is that these endpoints will be accepted as suitable for medication approval studies by the regulatory authorities and that understanding of the disease process will be improved.

Background. Currently, no validated clinical endpoints for treatment studies exist for intermediate age-related macular degeneration (iAMD). Objective. The European MACUSTAR study aims to develop and clinically validate adequate clinical endpoints for future treatment studies in iAMD and to identify early determinants of disease progression to late stage AMD. Material and methods. The MACUSTAR study protocol was developed by an international consortium of researchers from academia, the pharmaceutical industry and medical device companies. The MACUSTAR project is funded by the Innovative Medicines Initiative 2 (IMI2) of the European Union. Results. The MACUSTAR study consists of a cross-sectional and a longitudinal investigation. A total of 750 subjects with early, intermediate and late AMD as well as control subjects with no signs of AMD will be included with a follow-up period of 3 years. Overall, 20 European study centers are involved. Conclusion. The MACUSTAR project will generate large high-quality datasets, which will allow clinical validation of novel endpoints for future interventional trials in iAMD. The aim is that these endpoints will be accepted as suitable for medication approval studies by the regulatory authorities and that understanding of the disease process will be improved.

16 páginas, 5 figuras ; Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease. ; The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria "La Caixa", Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—"Una manera de hacer Europa"). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). 100-Plus study: We are grateful for the collaborative efforts of all participating centenarians and their family members and/or relations. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The authors are grateful to all LASA participants, the fieldwork team and all researchers for their ongoing commitment to the study. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Genotyping of the German case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND (German Federal Ministry of Education and Research, BMBF: 01ED1619A). Full acknowledgments for the studies that contributed data can be found in the Supplementary Note. We thank the numerous participants, researchers, and staff from many studies who collected and contributed to the data. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i–Select chips was funded by the French National Foundation on AD and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer's Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC–10–196728. This research has been conducted using the UK Biobank public resource obtained through the University of Edinburg Data Share (https://datashare.is.ed.ac.uk/handle/10283/3364). ; Peer reviewed