Bayesian Optimal Design for Ordinary Differential Equation Models

Bayesian optimal design is considered for experiments where it is hypothesised that the responses are described by the intractable solution to a system of non-linear ordinary differential equations (ODEs). Bayesian optimal design is based on the minimisation of an expected loss function where the expectation is with respect to all unknown quantities (responses and parameters). This expectation is typically intractable even for simple models before even considering the intractability of the ODE solution. New methodology is developed for this problem that involves minimising a smoothed stochastic approximation to the expected loss and using a state-of-the-art stochastic solution to the ODEs, by treating the ODE solution as an unknown quantity. The methodology is demonstrated on three illustrative examples and a real application involving estimating the properties of human placentas

Bayesian Optimal Design for Ordinary Differential Equation Models

Bayesian optimal design is considered for experiments where it is hypothesised that the responses are described by the intractable solution to a system of non-linear ordinary differential equations (ODEs). Bayesian optimal design is based on the minimisation of an expected loss function where the expectation is with respect to all unknown quantities (responses and parameters). This expectation is typically intractable even for simple models before even considering the intractability of the ODE solution. New methodology is developed for this problem that involves minimising a smoothed stochastic approximation to the expected loss and using a state-of-the-art stochastic solution to the ODEs, by treating the ODE solution as an unknown quantity. The methodology is demonstrated on three illustrative examples and a real application involving estimating the properties of human placentas

The structures of secretory and dimeric immunoglobulin A

Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions

Mapping the Asymmetric Thick Disk I. A Search for Triaxiality

A significant asymmetry in the distribution of faint blue stars in the inner Galaxy, Quadrant 1 (l = 20 to 45 degrees) compared to Quadrant 4 was first reported by Larsen & Humphreys (1996). Parker et al (2003, 2004) greatly expanded the survey to determine its spatial extent and shape and the kinematics of the affected stars. This excess in the star counts was subsequently confirmed by Juric et al. (2008) using SDSS data. Possible explanations for the asymmetry include a merger remnant, a triaxial Thick Disk, and a possible interaction with the bar in the Disk. In this paper we describe our program of wide field photometry to map the asymmetry to fainter magnitudes and therefore larger distances. To search for the signature of triaxiality, we extended our survey to higher Galactic longitudes. We find no evidence for an excess of faint blue stars at l > 55 degrees including the faintest magnitude interval. The asymmetry and star count excess in Quadrant 1 is thus not due to a triaxial Thick Disk.Comment: 36 pages, 8 figures. Accepted by Astronomical Journa

Symmetry-mode analysis for local structure investigations using pair distribution function data

Symmetry-adapted distortion modes provide a natural way to describe distorted structures derived from higher-symmetry parent phases. Structural refinements using symmetry-mode amplitudes as fit variables have been used for at least 10 years in Rietveld refinements of the average crystal structure from diffraction data; more recently, this approach has also been used for investigations of the local structure using real-space pair distribution function (PDF) data. Here, we further demonstrate the value of performing symmetry-mode fits to PDF data through the successful application of this method to two topical materials: TiSe$_2$, where we detect the subtle but long-range structural distortion driven by the formation of a charge density wave, and MnTe, where we characterize a large but highly localized structural distortion in terms of symmetry-lowering displacements of the Te atoms. The analysis is performed using fully open-source code within the DiffPy framework using two packages we developed for this work: isopydistort, which provides a scriptable interface to the ISODISTORT web application for group theoretical calculations, and isopytools, which converts the ISODISTORT output into a DiffPy-compatible format for subsequent fitting and analysis. These developments expand the potential impact of symmetry-adapted PDF analysis by enabling high throughput analysis and removing the need for any commercial software

Mapping the Asymmetric Thick Disk: II Distance, Size and Mass of the Hercules Thick Disk Cloud

The Hercules Thick Disk Cloud (Larsen et al. 2008) was initially discovered as an excess in the number of faint blue stars between quadrants 1 and 4 of the Galaxy. The origin of the Cloud could be an interaction with the disk bar, a triaxial thick disk or a merger remnant or stream. To better map the spatial extent of the Cloud along the line of sight, we have obtained multi-color UBVR photometry for 1.2 million stars in 63 fields approximately 1 square degree each. Our analysis of the fields beyond the apparent boundaries of the excess have already ruled out a triaxial thick disk as a likely explanation (Larsen, Humphreys and Cabanela 2010) In this paper we present our results for the star counts over all of our fields, determine the spatial extent of the over density across and along the line of sight, and estimate the size and mass of the Cloud. Using photometric parallaxes, the stars responsible for the excess are between 1 and 6 kiloparsecs from the Sun, 0.5 -- 4 kpc above the Galactic plane, and extends approximately 3-4 kiloparsecs across our line of sight. It is thus a major substructure in the Galaxy. The distribution of the excess along our sight lines corresponds with the density contours of the bar in the Disk, and its most distant stars are directly over the bar. We also see through the Cloud to its far side. Over the entire 500 square degrees of sky containing the Cloud, we estimate more than 5.6 million stars and 1.9 million solar masses of material. If the over density is associated with the bar, it would exceed 1.4 billion stars and more than than 50 million solar masses. Finally, we argue that the Hercules-Aquila Cloud (Belokurov et al. 2007) is actually the Hercules Thick Disk Cloud.Comment: 52 pages, 13 figure

Economic outcomes associated with deep surgical site infection in patients with an open fracture of the lower limb

Aims The aim of this study was to estimate economic outcomes associated with deep surgical site infection (SSI) in patients with an open fracture of the lower limb. Patients and Methods A total of 460 patients were recruited from 24 specialist trauma hospitals in the United Kingdom Major Trauma Network. Preference-based health-related quality-of-life outcomes, assessed using the EuroQol EQ-5D-3L and the 6-Item Short-Form Health Survey questionnaire (SF-6D), and economic costs (£, 2014/2015 prices) were measured using participant-completed questionnaires over the 12 months following injury. Descriptive statistics and multivariate regression analysis were used to explore the relationship between deep SSI and health utility scores, quality-adjusted life-years (QALYs), and health and personal social service (PSS) costs. Results Deep SSI was associated with lower EQ-5D-3L derived QALYs (adjusted mean difference -0.102, 95% confidence interval (CI) -0.202 to 0.001, p = 0.047) and increased health and social care costs (adjusted mean difference £1950; 95% CI £1383 to £5285, p = 0.250) versus patients without deep SSI over the 12 months following injury. Conclusion Deep SSI may lead to significantly impaired health-related quality of life and increased economic costs. Our economic estimates can be used to inform clinical and budgetary service planning and can act as reference data for future economic evaluations of preventive or treatment interventions

The discomforting rise of ' public geographies': a 'public' conversation.

In this innovative and provocative intervention, the authors explore the burgeoning ‘public turn’ visible across the social sciences to espouse the need to radically challenge and reshape dominant and orthodox visions of ‘the academy’, academic life, and the role and purpose of the academic

Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types

Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear