Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted.

BACKGROUND: Introduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme. METHODS: We used primary care data from the Clinical Practice Research Datalink and age-stratified time-series analyses to derive adjusted incidence rate ratios (IRRa) for AGE in the first two years of the post-vaccination era (July 2013-April 2015) compared to the pre-vaccination era (July 2008-June 2013). We estimated cases averted among children aged <5years in the first year of the vaccination programme by comparing observed numbers of AGE cases in 2013-2014 to numbers predicted from the time-series models. We then estimated the healthcare costs averted for general practice consultations, ED visits and hospitalisations. RESULTS: In general practice, AGE rates in infants (the target group for vaccination) decreased by 15% overall after vaccine introduction (IRRa=0.85; 95%CI=0.76-0.95), and by 41% in the months of historically high rotavirus circulation (IRRa=0.59; 95%CI=0.53-0.66). Rates also decreased in other young children and to a lesser degree in older individuals, indicating herd immunity. Across all three settings (general practice, EDs, and hospitalisations) an estimated 87,376 (95% prediction interval: 62,588-113,561) AGE visits by children aged <5years were averted in 2013-14, associated with an estimated £12.5million (9,209-16,198) reduction in healthcare costs. CONCLUSIONS: The marked decreases in the general practice AGE burden after rotavirus vaccine introduction mirror decreases seen in other UK healthcare settings. Overall, these decreases are associated with substantial averted healthcare costs

Inverse Estimation of an Annual Cycle of California's Nitrous Oxide Emissions

Nitrous oxide (N_2O) is a potent long‐lived greenhouse gas (GHG) and the strongest current emissions of global anthropogenic stratospheric ozone depletion weighted by its ozone depletion potential. In California, N_2O is the third largest contributor to the state's anthropogenic GHG emission inventory, though no study has quantified its statewide annual emissions through top‐down inverse modeling. Here we present the first annual (2013–2014) statewide top‐down estimates of anthropogenic N_2O emissions. Utilizing continuous N_2O observations from six sites across California in a hierarchical Bayesian inversion, we estimate that annual anthropogenic emissions are 1.5–2.5 times (at 95% confidence) the state inventory (41 Gg N_2O in 2014). Without mitigation, this estimate represents 4–7% of total GHG emissions assuming that other reported GHG emissions are reasonably correct. This suggests that control of N_2O could be an important component in meeting California's emission reduction goals of 40% and 80% below 1990 levels of the total GHG emissions (in CO_2 equivalent) by 2030 and 2050, respectively. Our seasonality analysis suggests that emissions are similar across seasons within posterior uncertainties. Future work is needed to provide source attribution for subregions and further characterization of seasonal variability

A unified framework for the Kondo problem and for an impurity in a Luttinger liquid

We develop a unified theoretical framework for the anisotropic Kondo model and the boundary sine-Gordon model. They are both boundary integrable quantum field theories with a quantum-group spin at the boundary which takes values, respectively, in standard or cyclic representations of the quantum group $SU(2)_q$. This unification is powerful, and allows us to find new results for both models. For the anisotropic Kondo problem, we find exact expressions (in the presence of a magnetic field) for all the coefficients in the ``Anderson-Yuval'' perturbative expansion. Our expressions hold initially in the very anisotropic regime, but we show how to continue them beyond the Toulouse point all the way to the isotropic point using an analog of dimensional regularization. For the boundary sine-Gordon model, which describes an impurity in a Luttinger liquid, we find the non-equilibrium conductance for all values of the Luttinger coupling.Comment: 36 pages (22 in double-page format), 7 figures in uuencoded file, uses harvmac and epsf macro

Three aromatic residues are required for electron transfer during iron mineralization in Bacterioferritin

Ferritins are iron storage proteins that overcome problems of toxicity and poor bioavailability of iron by catalysing iron oxidation and mineralization through the activity of a diiron ferroxidase site. Unlike in other ferritins, the oxidized di-Fe3+ site of Escherichia coli bacterioferritin (EcBFR) is stable and therefore does not function as a conduit for the transfer of Fe3+ into the storage cavity, but instead acts as a true catalytic cofactor that cycles its oxidation state while driving Fe2+ oxidation in the cavity. Here we demonstrate that EcBFR mineralization depends on three near-diiron site aromatic residues, Tyr25, Tyr58 and Trp133, and that a transient radical is formed on Tyr25. The data indicate that the aromatic residues, together with a previously identified inner surface iron site, promote mineralization by ensuring the simultaneous delivery of two electrons, derived from Fe2+ oxidation in the BFR cavity, to the di-ferric catalytic site for safe reduction of O2

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Bacterial Transmembrane Proteins that Lack N-Terminal Signal Sequences

Tail-anchored membrane proteins (TAMPs), a class of proteins characterized by their lack of N-terminal signal sequence and Sec-independent membrane targeting, play critical roles in apoptosis, vesicle trafficking and other vital processes in eukaryotic organisms. Until recently, this class of membrane proteins has been unknown in bacteria. Here we present the results of bioinformatic analysis revealing proteins that are superficially similar to eukaryotic TAMPs in the bacterium Streptomyces coelicolor. We demonstrate that at least four of these proteins are bona fide membrane-spanning proteins capable of targeting to the membrane in the absence of their N-terminus and the C-terminal membrane-spanning domain is sufficient for membrane targeting. Several of these proteins, including a serine/threonine kinase and the SecE component of the Sec translocon, are widely conserved in bacteria

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Global, regional, and national estimates of tuberculosis incidence and case detection among incarcerated individuals from 2000 to 2019: a systematic analysis.

People who are incarcerated are at high risk of developing tuberculosis. We aimed to estimate the annual global, regional, and national incidence of tuberculosis among incarcerated populations from 2000 to 2019. We collected and aggregated data for tuberculosis incidence and prevalence estimates among incarcerated individuals in published and unpublished literature, annual tuberculosis notifications among incarcerated individuals at the country level, and the annual number of incarcerated individuals at the country level. We developed a joint hierarchical Bayesian meta-regression framework to simultaneously model tuberculosis incidence, notifications, and prevalence from 2000 to 2019. Using this model, we estimated trends in absolute tuberculosis incidence and notifications, the incidence and notification rates, and the case detection ratio by year, country, region, and globally. In 2019, we estimated a total of 125 105 (95% credible interval [CrI] 93 736-165 318) incident tuberculosis cases among incarcerated individuals globally. The estimated incidence rate per 100 000 person-years overall was 1148 (95% CrI 860-1517) but varied greatly by WHO region, from 793 (95% CrI 430-1342) in the Eastern Mediterranean region to 2242 (1515-3216) in the African region. Global incidence per 100 000 person-years between 2000 and 2012 among incarcerated individuals decreased from 1884 (95% CrI 1394-2616) to 1205 (910-1615); however, from 2013 onwards, tuberculosis incidence per 100 000 person-years was stable, from 1183 (95% CrI 876-1596) in 2013 to 1148 (860-1517) in 2019. In 2019, the global case detection ratio was estimated to be 53% (95% CrI 42-64), the lowest over the study period. Our estimates suggest a high tuberculosis incidence rate among incarcerated individuals globally with large gaps in tuberculosis case detection. Tuberculosis in incarcerated populations must be addressed with interventions specifically tailored to improve diagnoses and prevent transmission as a part of the broader global tuberculosis control effort. National Institutes of Health. [Abstract copyright: This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.