Mendelian randomisation identifies priority groups for prophylactic EBV vaccination

BACKGROUND: Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin’s, non-Hodgkin’s lymphomas, and multiple sclerosis. There is substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors—sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV. METHODS: We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal. RESULTS: Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus. CONCLUSIONS: Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced

Hydrology

DTFH61-83-C-00118This manual provides a synthesis of practical hydrologic methods and techniques to assist the highway engineer in the analysis and design of highway drainage structures. The manual begins with a discussion of descriptive hydrology, the surface runoff process and hydrologic data with emphasis given to the highway stream-crossing problem. The commonly used frequency distributions for estimating peak flows for basins with adequate data are discussed in detail and illustrated by examples. USGS regional regression equations and other methods for peak flow determinations in ungaged watersheds and in basins with insufficient data are presented with examples. Methods for developing unit hydrographs from streamflow data and by the Snyder and SCS synthetic procedures for ungaged sites are described in detail. Techniques for developing design storms and design hydrographs are given for basins with and without data. The Muskingum method for routing of hydrographs in channels and the Storage-Indication method for storage routing at highway embankments are discussed with illustrative examples. Estimates of peak flow and hydrograph development in urban watersheds using the SCS methods of TR-55 and the USGS Basin Development Factor procedure are illustrated in detail. The manual concludes with a brief discussion of risk analysis and its dependence on hydrologic analysis

Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation