Joint profiling of DNA methylation and chromatin architecture in single cells.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues

The use of continuous electronic prescribing data to infer trends in antimicrobial consumption and estimate the impact of stewardship interventions in hospitalized children.

BACKGROUND: Understanding antimicrobial consumption is essential to mitigate the development of antimicrobial resistance, yet robust data in children are sparse and methodologically limited. Electronic prescribing systems provide an important opportunity to analyse and report antimicrobial consumption in detail. OBJECTIVES: We investigated the value of electronic prescribing data from a tertiary children's hospital to report temporal trends in antimicrobial consumption in hospitalized children and compare commonly used metrics of antimicrobial consumption. METHODS: Daily measures of antimicrobial consumption [days of therapy (DOT) and DDDs] were derived from the electronic prescribing system between 2010 and 2018. Autoregressive moving-average models were used to infer trends and the estimates were compared with simulated point prevalence surveys (PPSs). RESULTS: More than 1.3 million antimicrobial administrations were analysed. There was significant daily and seasonal variation in overall consumption, which reduced annually by 1.77% (95% CI 0.50% to 3.02%). Relative consumption of meropenem decreased by 6.6% annually (95% CI -3.5% to 15.8%) following the expansion of the hospital antimicrobial stewardship programme. DOT and DDDs exhibited similar trends for most antimicrobials, though inconsistencies were observed where changes to dosage guidelines altered consumption calculation by DDDs, but not DOT. PPS simulations resulted in estimates of change over time, which converged on the model estimates, but with much less precision. CONCLUSIONS: Electronic prescribing systems offer significant opportunities to better understand and report antimicrobial consumption in children. This approach to modelling administration data overcomes the limitations of using interval data and dispensary data. It provides substantially more detailed inferences on prescribing patterns and the potential impact of stewardship interventions

SUPPORT Tools for evidence-informed health Policymaking (STP) 8: Deciding how much confidence to place in a systematic review

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high <sup>3</sup>He/<sup>4</sup>He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic <sup>3</sup>He/<sup>4</sup>He ratios yet recorded. A strong correlation between <sup>3</sup>He/<sup>4</sup>He and <sup>87</sup>Sr/<sup>86</sup>Sr, <sup>143</sup>Nd/<sup>144</sup>Nd and trace element ratios demonstrate that the <sup>3</sup>He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest <sup>3</sup>He/<sup>4</sup>He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a <sup>3</sup>He-recharged depleted mantle (HRDM) reservoir may be the principal source of high <sup>3</sup>He/<sup>4</sup>He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

Gluon-gluon contributions to W+ W- production and Higgs interference effects

In this paper we complete our re-assessment of the production of W boson pairs at the LHC, by calculating analytic results for the gg -> W+ W- -> (\nu l l\nu) process including the effect of massive quarks circulating in the loop. Together with the one-loop amplitudes containing the first two generations of massless quarks propagating in the loop, these diagrams can give a significant contribution with a large flux of gluons. One of the component parts of this calculation is the production of a standard model Higgs boson, gg -> H and its subsequent decay, H -> W+(-> \nu l) W-(-> l \nu). We will quantify the importance of the interference between the Higgs boson production process and the gluon-induced continuum production in the context of searches for the Higgs boson at the Tevatron and the LHC. For instance, for mH < 140 GeV the effect of the interference typically results in around a 10% reduction in the expected number of Higgs signal events. The majority of this interference is due to non-resonant contributions. Therefore cuts on the transverse mass such as those currently used by the ATLAS collaboration reduce the destructive interference to about a 1% effect. We advocate that a cut on the maximum transverse mass be used in future Higgs searches in this channel

Automation of one-loop QCD corrections

We present the complete automation of the computation of one-loop QCD corrections, including UV renormalization, to an arbitrary scattering process in the Standard Model. This is achieved by embedding the OPP integrand reduction technique, as implemented in CutTools, into the MadGraph framework. By interfacing the tool so constructed, which we dub MadLoop, with MadFKS, the fully automatic computation of any infrared-safe observable at the next-to-leading order in QCD is attained. We demonstrate the flexibility and the reach of our method by calculating the production rates for a variety of processes at the 7 TeV LHC.Comment: 64 pages, 12 figures. Corrected the value of m_Z in table 1. In table 2, corrected the values of cross sections in a.4 and a.5 (previously computed with mu=mtop/2 rather than mu=mtop/4). In table 2, corrected the values of NLO cross sections in b.3, b.6, c.3, and e.7 (the symmetry factor for a few virtual channels was incorrect). In sect. A.4.3, the labeling of the four-momenta was incorrec

NLO Higgs boson production plus one and two jets using the POWHEG BOX, MadGraph4 and MCFM

We present a next-to-leading order calculation of Higgs boson production plus one and two jets via gluon fusion interfaced to shower Monte Carlo programs, implemented according to the POWHEG method. For this implementation we have used a new interface of the POWHEG BOX with MadGraph4, that generates the codes for generic Born and real processes automatically. The virtual corrections have been taken from the MCFM code. We carry out a simple phenomenological study of our generators, comparing them among each other and with fixed next-to-leading order results.Comment: 27 pages, 21 figure

Waiting time distribution in public health care: empirics and theory

Excessive waiting times for elective surgery have been a long-standing concern in many national healthcare systems in the OECD. How do the hospital admission patterns that generate waiting lists affect different patients? What are the hospitals characteristics that determine waiting times? By developing a model of healthcare provision and analysing empirically the entire waiting time distribution we attempt to shed some light on those issues. We first build a theoretical model that describes the optimal waiting time distribution for capacity constraint hospitals. Secondly, employing duration analysis, we obtain empirical representations of that distribution across hospitals in the UK from 1997–2005. We observe important differences on the ‘scale’ and on the ‘shape’ of admission rates. Scale refers to how quickly patients are treated and shape represents trade-offs across duration-treatment profiles. By fitting the theoretical to the empirical distributions we estimate the main structural parameters of the model and are able to closely identify the main drivers of these empirical differences. We find that the level of resources allocated to elective surgery (budget and physical capacity), which determines how constrained the hospital is, explains differences in scale. Changes in benefits and costs structures of healthcare provision, which relate, respectively, to the desire to prioritise patients by duration and the reduction in costs due to delayed treatment, determine the shape, affecting short and long duration patients differently