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Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene. ; The study was supported by grants provided by the Swedish Cancer Society (Cancerfonden), the Stockholm County Council (ALF project), the Swedish Research Council (Vetenskapsrådet), the Stockholm Cancer Society (Radiumhemsfonderna) and Bert von Kantzows and Nilsson-Ehle's foundations. BCAC is funded by Cancer Research UK (C1287/A16563, C1287/A10118), the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. Funding of individual BCAC studies is listed in the Supplemental Note.

Shanghai city has been suffering land subsidence caused by overly exploitation of ground water since 1921, which is a serious problem for this coastal city with altitude of 2.2–4.8 m above mean sea level. The largest cumulative land subsidence amounted to 2.6 m in the downtown area. Measures to decrease the ground water exploitation, change the pumping aquifers, and increase aquifer artificial recharge have been used to mitigate land subsidence since 1961. It is necessary to develop a proper numerical model to simulate and predict land subsidence. In this study, a decoupled three-dimensional (3-D) finite element land subsidence model including a 3-D ground water flow model and a 3-D geo-mechanical model was developed to simulate the 3-D deformation of the aquifer systems in the center area of Shanghai. The area of downtown Shanghai is 660 km 2 , with 10 million inhabitants, dense high buildings, and 11 metro lines. The simulation spans the period from 1979 to 1995. Two different assumptions have been tested on the side boundary, i.e., precluding the three components of the displacement, or assuming a free-displacement condition. The distribution of calculated land subsidence and horizontal displacements in different aquifers was analyzed. The computed vertical displacement fitted well with the available observations. It has been verified that the two different assumptions on the lateral boundaries in the geo-mechanical model caused different results just limited on nodes close to boundary. The developed 3-D land subsidence model is reasonable and can be used to simulate and predict 3-D movement of aquifer systems in the center area of Shanghai, which could provide scientific support to local government in controlling land subsidence and differential movements of the land surface.

Shanghai city has been suffering land subsidence caused by overly exploitation of ground water since 1921, which is a serious problem for this coastal city with altitude of 2.2–4.8 m above mean sea level. The largest cumulative land subsidence amounted to 2.6 m in the downtown area. Measures to decrease the ground water exploitation, change the pumping aquifers, and increase aquifer artificial recharge have been used to mitigate land subsidence since 1961. It is necessary to develop a proper numerical model to simulate and predict land subsidence. In this study, a decoupled three-dimensional (3-D) finite element land subsidence model including a 3-D ground water flow model and a 3-D geo-mechanical model was developed to simulate the 3-D deformation of the aquifer systems in the center area of Shanghai. The area of downtown Shanghai is 660 km2, with 10 million inhabitants, dense high buildings, and 11 metro lines. The simulation spans the period from 1979 to 1995. Two different assumptions have been tested on the side boundary, i.e., precluding the three components of the displacement, or assuming a free-displacement condition. The distribution of calculated land subsidence and horizontal displacements in different aquifers was analyzed. The computed vertical displacement fitted well with the available observations. It has been verified that the two different assumptions on the lateral boundaries in the geo-mechanical model caused different results just limited on nodes close to boundary. The developed 3-D land subsidence model is reasonable and can be used to simulate and predict 3-D movement of aquifer systems in the center area of Shanghai, which could provide scientific support to local government in controlling land subsidence and differential movements of the land surface.

We are grateful to Hanne Nørgaard Nielsen, Christina Aaby Svendsen, Jacob Dyring Jensen, Birthe S. Rosenqvist Lund, Kate Vina Vibefeldt, Inge Marianne Hansen, Gunhild Larsen, Hanne Mordhorst, and Carsten Bidstrup for technical assistance. We also thank Jeffrey Edward Skiby for internal review. This study has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 643476 (COMPARE), the World Health Organization, The Villum Foundation (VKR023052), and The Novo Nordisk Foundation (NNF16OC0021856: Global Surveillance of Antimicrobial Resistance). ; Altres ajuts: VF/VKR023052 ; Altres ajuts: GSAR/NNF16OC0021856 ; Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.