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Snus is an oral smokeless tobacco product which is usually placed behind the upper lip, either in a loose form or in portioned sachets, and is primarily used in Sweden and Norway. The purpose of this review is to examine the reported effects of snus use in relation to specified health effects, namely lung cancer, cardiovascular disease, pancreatic cancer, diabetes, oral cancer and non-neoplastic oral disease. The review also examines the harm reduction potential of snus as an alternative to cigarettes by comparing the prevalence of snus use and cigarette smoking, and the reported incidence of tobacco-related diseases across European Union countries. The scientific literature generally indicates that the use of snus is not a significant risk factor for developing lung cancer, cardiovascular disease, pancreatic cancer or oral cancer. Studies investigating snus use and diabetes have reported that high consumption of snus (estimated as being four or more cans per week) may be associated with a higher risk of developing diabetes or components of metabolic syndrome; however, overall results are not conclusive. Snus use is associated with the presence of non-neoplastic oral mucosal lesions which are reported to heal rapidly once use has stopped. The most recent Eurobarometer data from 2017 reported that Sweden had the lowest prevalence of daily cigarette use in the European Union at 5% whilst daily "oral tobacco" use was reported to be 20%. European data published by the World Health Organisation in 2018 indicated that Sweden had the lowest rate of tobacco-related mortality and the lowest incidence of male lung cancer. Overall, prevalence statistics and epidemiological data indicate that the use of snus confers a significant harm reduction benefit which is reflected in the comparatively low levels of tobacco-related disease in Sweden when compared with the rest of Europe. The available scientific data, including long-term population studies conducted by independent bodies, demonstrates that the health risks associated with snus are considerably lower than those associated with cigarette smoking.

Background: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. Results: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved > 2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. Conclusions: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture. ; This work has been funded by INRAE (France) and by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 764840 for the ITN IGNITE project. Rosa Fernandez was funded by a Juan de la Cierva-Incorporación Fellowship (Government of Spain, IJCI-2015-26627) and a Marie Skłodowska-Curie Fellowship (747607). Angela Douglas was supported by the US National Institute of Food and Agriculture Grant 12216941. Honglin Feng was supported by a University of Miami Maytag Fellowship, William H. Evoy Graduate Research Support Fund, and a Molecular Biosciences Graduate Research Award from the Department of Biology.

Funding Information: The CMB-S4 collaboration ( https://cmb-s4.org/ ) is working to plan, construct, and operate a next-generation, multisite CMB experiment in the 2020s. The collaboration is led by an elected Governing Board, Spokespeople, Committee Chairs, and Executive Team. Funding for the CMB-S4 Integrated Project Office is provided by the Department of Energy's Office of Science (project level CD-0) and by the National Science Foundation through the Mid-Scale Research Infrastructure-R1 award OPP-1935892. This research used resources of Argonne National Laboratory, a U.S. Department of Energy (DOE) Office of Science User Facility operated under Contract No. DE-AC02-06CH11357. This document was prepared by the CMB-S4 collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. Work at Lawrence Berkeley National Laboratory was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Work at SLAC National Accelerator Laboratory is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. In the United States, work on CMB-S4 by individual investigators has been supported by the National Science Foundation (awards 1248097, 1255358, 1815887, 1835865, 1852617, 2009469), the Department of Energy (awards DE-SC0009919, DE-SC0009946, DE-SC0010129, DE-SC0011784), and the National Aeronautics and Space Administration (award ATP-80NSSC20K0518). In Australia, the Melbourne authors acknowledge support from an Australian Research Council Future Fellowship (FT150100074). In Canada, R.H. is supported by the Discovery Grants program from NSERC, and acknowledges funding from CIFAR, the Sloan Foundation, and the Dunlap family. In Italy, C.B. acknowledges support under the ASI COSMOS and INFN INDARK programs. In the Netherlands, D.M. acknowledges NWO VIDI award number 639.042.730. In Switzerland, J.C. is supported by an SNSF Eccellenza Professorial Fellowship (No. 186879). In the United Kingdom, A.L., G.F., and J.C. are supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant Agreement No. [616170]. A.L. also acknowledges STFC award ST/P000525/1. S.M. is supported by the research program Innovational Research Incentives Scheme (Vernieuwingsimpuls), which is financed by the Netherlands Organization for Scientific Research through the NWO VIDI grant No. 639.042.612-Nissanke and the Labex ILP (reference ANR-10-LABX-63) part of the Idex SUPER, received financial state aid managed by the Agence Nationale de la Recherche,as part of the program Investissements d'avenir under the reference ANR-11-IDEX-0004-02. Some computations in this paper were run on the Odyssey cluster, supported by the FAS Science Division Research Computing Group at Harvard University. Publisher Copyright: © 2022. The Author(s). Published by the American Astronomical Society. ; CMB-S4-the next-generation ground-based cosmic microwave background (CMB) experiment-is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2-3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5 sigma, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL. ; Peer reviewed