Background and aims Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10−38). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. Conclusions The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.

This Report summarizes the results of the activities of the LHC Higgs Cross Section Working Group in the period 2014-2016. The main goal of the working group was to present the state-of-the-art of Higgs physics at the LHC, integrating all new results that have appeared in the last few years. The first part compiles the most up-to-date predictions of Higgs boson production cross sections and decay branching ratios, parton distribution functions, and off-shell Higgs boson production and interference effects. The second part discusses the recent progress in Higgs effective field theory predictions, followed by the third part on pseudo-observables, simplified template cross section and fiducial cross section measurements, which give the baseline framework for Higgs boson property measurements. The fourth part deals with the beyond the Standard Model predictions of various benchmark scenarios of Minimal Supersymmetric Standard Model, extended scalar sector, Next-to-Minimal Supersymmetric Standard Model and exotic Higgs boson decays. This report follows three previous working-group reports: Handbook of LHC Higgs Cross Sections: 1. Inclusive Observables (CERN-2011-002), Handbook of LHC Higgs Cross Sections: 2. Differential Distributions (CERN-2012-002), and Handbook of LHC Higgs Cross Sections: 3. Higgs properties (CERN-2013-004). The current report serves as the baseline reference for Higgs physics in LHC Run 2 and beyond.

Future wireless networks are expected to constitute a distributed intelligent wireless communications, sensing, and computing platform, which will have the challenging requirement of interconnecting the physical and digital worlds in a seamless and sustainable manner. Currently, two main factors prevent wireless network operators from building such networks: (1) the lack of control of the wireless environment, whose impact on the radio waves cannot be customized, and (2) the current operation of wireless radios, which consume a lot of power because new signals are generated whenever data has to be transmitted. In this paper, we challenge the usual “more data needs more power and emission of radio waves” status quo, and motivate that future wireless networks necessitate a smart radio environment: a transformative wireless concept, where the environmental objects are coated with artificial thin films of electromagnetic and reconfigurable material (that are referred to as reconfigurable intelligent meta-surfaces), which are capable of sensing the environment and of applying customized transformations to the radio waves. Smart radio environments have the potential to provide future wireless networks with uninterrupted wireless connectivity, and with the capability of transmitting data without generating new signals but recycling existing radio waves. We will discuss, in particular, two major types of reconfigurable intelligent meta-surfaces applied to wireless networks. The first type of meta-surfaces will be embedded into, e.g., walls, and will be directly controlled by the wireless network operators via a software controller in order to shape the radio waves for, e.g., improving the network coverage. The second type of meta-surfaces will be embedded into objects, e.g., smart t-shirts with sensors for health monitoring, and will backscatter the radio waves generated by cellular base stations in order to report their sensed data to mobile phones. These functionalities will enable wireless network operators to offer new services without the emission of additional radio waves, but by recycling those already existing for other purposes. This paper overviews the current research efforts on smart radio environments, the enabling technologies to realize them in practice, the need of new communication-theoretic models for their analysis and design, and the long-term and open research issues to be solved towards their massive deployment. In a nutshell, this paper is focused on discussing how the availability of reconfigurable intelligent meta-surfaces will allow wireless network operators to redesign common and well-known network communication paradigms.

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) : Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection. Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Abstract Background falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. Objectives to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. Methods a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. Recommendations all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. Conclusions the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Two-dimensional semiconductors such as MoS2 are an emerging material family with wide-ranging potential applications in electronics, optoelectronics, and energy harvesting. Large-area growth methods are needed to open the way to applications. Control over lattice orientation during growth remains a challenge. This is needed to minimize or even avoid the formation of grain boundaries, detrimental to electrical, optical, and mechanical properties of MoS2 and other 2D semiconductors. Here, we report on the growth of high-quality monolayer MoS2 with control over lattice orientation. We show that the monolayer film is composed of coalescing single islands with limited numbers of lattice orientation due to an epitaxial growth mechanism. Optical absorbance spectra acquired over large areas show significant absorbance in the high-energy part of the spectrum, indicating that MoS2 could also be interesting for harvesting this region of the solar spectrum and fabrication of UV-sensitive photodetectors. Even though the interaction between the growth substrate and MoS2 is strong enough to induce lattice alignment via van der Waals interaction, we can easily transfer the grown material and fabricate devices. Local potential mapping along channels in field-effect transistors shows that the single-crystal MoS2 grains in our film are well connected, with interfaces that do not degrade the electrical conductivity. This is also confirmed by the relatively large and length-independent mobility in devices with a channel length reaching 80 μm.