Calibration of stochastic computer simulators using likelihood emulation

We calibrate a stochastic computer simulation model of ‘moderate’ computational expense. The simulator is an imperfect representation of reality, and we recognise this discrepancy to ensure a reliable calibration. The calibration model combines a Gaussian process emulator of the likelihood surface with importance sampling. Changing the discrepancy specification changes only the importance weights, which lets us investigate sensitivity to different discrepancy specifications at little computational cost. We present a case study of a natural history model that has been used to characterise UK bowel cancer incidence. Data sets and computer code are provided as supplementary material

IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity.

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β(-/-)), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity

evgam: An R Package for Generalized Additive Extreme Value Models

This article introduces the R package evgam. The package provides functions for fitting extreme value distributions. These include the generalized extreme value and generalized Pareto distributions. The former can also be fitted through a point process representation. Package evgam supports quantile regression via the asymmetric Laplace distribution, which can be useful for estimating high thresholds, sometimes used to discriminate between extreme and non-extreme values. The main addition of package evgam is to let extreme value distribution parameters have generalized additive model forms, the smoothness of which can be objectively estimated using Laplace's method. Illustrative examples fitting various distributions with various specifications are given. These include daily precipitation accumulations for part of Colorado, US, used to illustrate spatial models, and daily maximum temperatures for Fort Collins, Colorado, US, used to illustrate temporal models

Calibration of Stochastic Computer Simulators Using Likelihood Emulation

<p>We calibrate a stochastic computer simulation model of “moderate” computational expense. The simulator is an imperfect representation of reality, and we recognize this discrepancy to ensure a reliable calibration. The calibration model combines a Gaussian process emulator of the likelihood surface with importance sampling. Changing the discrepancy specification changes only the importance weights, which lets us investigate sensitivity to different discrepancy specifications at little computational cost. We present a case study of a natural history model that has been used to characterize UK bowel cancer incidence. Datasets and computer code are provided as supplementary material.</p

Measurement of charm fragmentation fractions in photoproduction at HERA

The production of D^0, D^*+, D^+, D_s+ and Lambda_c^+ charm hadrons and their antiparticles in ep scattering at HERA has been studied with the ZEUS detector, using a total integrated luminosity of 372 pb^-1. The fractions of charm quarks hadronising into a particular charm hadron were derived. In addition, the ratio of neutral to charged D-meson production rates, the fraction of charged D mesons produced in a vector state, and the stangeness-suppression factor have been determined. The measurements have been performed in the photoproduction regime. The charm hadrons were reconstructed in the range of transverse momentum p_T >3.8 GeV and pseudorapidity |eta|<1.6. The charm fragmentation fractions are compared to previous results from HERA and from e+e-experiments. The data support the hypothesis that fragmentation is independent of the production process