The impact of personalised risk information compared to a positive/negative result on informed choice and intention to undergo colonoscopy following colorectal Cancer screening in Scotland (PERICCS) - a randomised controlled trial:study protocol

Background In Scotland a new, easier to complete bowel screening test, the Faecal Immunochemical Test (FIT), has been introduced. This test gives more accurate information about an individual’s risk of having colorectal cancer (CRC), based on their age and gender, and could lead to fewer missed cancers compared to the current screening test. However, there is no evidence of the effect on colonoscopy uptake of providing individuals with personalised risk information following a positive FIT test. The objectives of the study are: 1) To develop novel methods of presenting personalised risk information in an easy-to-understand format using infographics with involvement of members of the public 2) To assess the impact of different presentations of risk information on informed choice and intention to take up an offer of colonoscopy after FIT 3) To assess participants’ responses to receiving personal risk information (knowledge, attitudes to screening/risk, emotional responses including anxiety). Methods Adults (age range 50–74) registered on the Scottish Bowel Screening database will be invited by letter to take part. Consenting participants will be randomised to one of three groups to receive hypothetical information about their risk of cancer, based on age, gender and faecal haemoglobin concentration: 1) personalised risk information in numeric form (e.g. 1 in 100) with use of infographics, 2) personalised information described as ‘highest’, ‘moderate’ or ‘lowest’ risk with use of infographics, and 3) as a ‘positive’ test result, as is current practice. Groups will be compared on informed choice, intention to have a colonoscopy, and satisfaction with their decision. Follow-up semi-structured qualitative interviews will be conducted, by telephone, with a small number of consenting participants (n = 10 per group) to explore the acceptability/readability and any potential negative impact of the risk information, participants’ understanding of risk factors, attitudes to the different scenarios, and reasons for reported intentions. Discussion Proving personalised risk information and allowing patient choice could lead to improved detection of CRC and increase patient satisfaction by facilitating informed choice over when/whether to undergo further invasive screening. However, we need to determine whether/how informed choice can be achieved and assess the potential impact on the colonoscopy service

Granular Packings: Nonlinear elasticity, sound propagation and collective relaxation dynamics

Experiments on isotropic compression of a granular assembly of spheres show that the shear and bulk moduli vary with the confining pressure faster than the 1/3 power law predicted by Hertz-Mindlin effective medium theories (EMT) of contact elasticity. Moreover, the ratio between the moduli is found to be larger than the prediction of the elastic theory by a constant value. The understanding of these discrepancies has been a longstanding question in the field of granular matter. Here we perform a test of the applicability of elasticity theory to granular materials. We perform sound propagation experiments, numerical simulations and theoretical studies to understand the elastic response of a deforming granular assembly of soft spheres under isotropic loading. Our results for the behavior of the elastic moduli of the system agree very well with experiments. We show that the elasticity partially describes the experimental and numerical results for a system under compressional loads. However, it drastically fails for systems under shear perturbations, particularly for packings without tangential forces and friction. Our work indicates that a correct treatment should include not only the purely elastic response but also collective relaxation mechanisms related to structural disorder and nonaffine motion of grains.Comment: 21 pages, 13 figure

Diagnostic accuracy of DXA compared to conventional spine radiographs for the detection of vertebral fractures in children

Objectives In children, radiography is performed to diagnose vertebral fractures and dual energy x-ray absorptiometry (DXA) to assess bone density. In adults, DXA assesses both. We aimed to establish whether DXA can replace spine radiographs in assessment of paediatric vertebral fractures. Methods Prospectively, lateral spine radiographs and lateral spine DXA of 250 children performed on the same day were independently scored by three radiologists using the simplified algorithm based qualitative technique and blinded to results of the other modality. Consensus radiograph read and second read of 100 random images were performed. Diagnostic accuracy, inter/intraobserver and intermodality agreements, patient/carer experience and radiation dose were assessed. Results Average sensitivity and specificity (95% confidence interval) in diagnosing one or more vertebral fractures requiring treatment was 70% (58%-82%) and 97% (94%- 100%) respectively for DXA and 74% (55%-93%) and 96% (95%-98%) for radiographs. Fleiss’ kappa for interobserver and average kappa for intraobserver reliability were 0.371 and 0.631 respectively for DXA and 0.418 and 0.621 for radiographs. Average effective dose was 41.9µSv for DXA and 232.7µSv for radiographs. Image quality was similar. Conclusion Given comparable image quality and non-inferior diagnostic accuracy, lateral spine DXA should replace conventional radiographs for assessment of vertebral fractures in children

Diagnosis of vertebral fractures in children: is a simplified algorithm-based qualitative technique reliable?

Background Identification of osteoporotic vertebral fractures allows treatment opportunity reducing future risk. There is no agreed standardised method for diagnosing paediatric vertebral fractures. Objective To evaluate the precision of a modified adult algorithm-based qualitative (ABQ) technique, applicable to children with primary or secondary osteoporosis. Materials and methods Three radiologists independently assessed lateral spine radiographs of 50 children with suspected reduction in bone mineral density using a modified ABQ scoring system and following simplification to include only clinically relevant parameters, a simplified ABQ score. A final consensus of all observers using simplified ABQ was performed as a reference standard for fracture characterisation. Kappa was calculated for interobserver agreement of the components of both scoring systems and intraobserver agreement of simplified ABQ based on a second read of 29 randomly selected images. Results Interobserver Kappa for modified ABQ scoring for fracture detection, severity and shape ranged from 0.34 to 0.49 Kappa for abnormal endplate and position assessment was 0.27 to 0.38. Inter- and intraobserver Kappa for simplified ABQ scoring for fracture detection and grade ranged from 0.37 to 0.46 and 0.45 to 0.56, respectively. Inter- and intraobserver Kappa for affected endplate ranged from 0.31 to 0.41 and 0.45 to 0.51, respectively. Subjectively, observers’ felt simplified ABQ was easier and less time-consuming. Conclusion Observer reliability of modified and simplified ABQ was similar, with slight to moderate agreement for fracture detection and grade/severity. Due to subjective preference for simplified ABQ, we suggest its use as a semi-objective measure of diagnosing paediatric vertebral fracture

Why Effective Medium Theory Fails in Granular Materials

Experimentally it is known that the bulk modulus, K, and shear modulus, \mu, of a granular assembly of elastic spheres increase with pressure, p, faster than the p^1/3 law predicted by effective medium theory (EMT) based on Hertz-Mindlin contact forces. To understand the origin of these discrepancies, we perform numerical simulations of granular aggregates under compression. We show that EMT can describe the moduli pressure dependence if one includes the increasing number of grain-grain contacts with p. Most important, the affine assumption (which underlies EMT), is found to be valid for K(p) but breakdown seriously for \mu(p). This explains why the experimental and numerical values of \mu(p) are much smaller than the EMT predictions.Comment: 4 pages, 5 figures, http://polymer.bu.edu/~hmaks

Pressure dependence of the sound velocity in a 2D lattice of Hertz-Mindlin balls: a mean field description

We study the dependence on the external pressure $P$ of the velocities $v_{L,T}$ of long wavelength sound waves in a confined 2D h.c.p. lattice of 3D elastic frictional balls interacting via one-sided Hertz-Mindlin contact forces, whose diameters exhibit mild dispersion. The presence of an underlying long range order enables us to build an effective medium description which incorporates the radial fluctuations of the contact forces acting on a single site. Due to the non linearity of Hertz elasticity, self-consistency results in a highly non-linear differential equation for the "equation of state" linking the effective stiffness of the array with the applied pressure, from which sound velocities are then obtained. The results are in excellent agreement with existing experimental results and simulations in the high and intermediate pressure regimes. It emerges from the analysis that the departure of $v_{L}(P)$ from the ideal $P^{1/6}$ Hertz behavior must be attributed primarily to the fluctuations of the stress field, rather than to the pressure dependence of the number of contacts

Excess AGN Activity in the z=2.30 Protocluster in HS 1700+64

We present the results of spectroscopic, narrow-band and X-ray observations of a z=2.30 protocluster in the field of the QSO HS 1700+643. Using a sample of BX/MD galaxies, which are selected to be at z~2.2-2.7 by their rest-frame ultraviolet colours, we find that there are 5 protocluster AGN which have been identified by characteristic emission-lines in their optical/near-IR spectra; this represents an enhancement over the field significant at ~98.5 per cent confidence. Using a ~200 ks Chandra/ACIS-I observation of this field we detect a total of 161 X-ray point sources to a Poissonian false-probability limit of 4x10^{-6} and identify 8 of these with BX/MD galaxies. Two of these are spectroscopically confirmed protocluster members and are also classified as emission-line AGN. When compared to a similarly selected field sample the analysis indicates this is also evidence for an enhancement of X-ray selected BX/MD AGN over the field, significant at ~99 per cent confidence. Deep Lya narrow-band imaging reveals that a total of 4/123 Lya emitters (LAEs) are found to be associated with X-ray sources, with two of these confirmed protocluster members and one highly likely member. We do not find a significant enhancement of AGN activity in this LAE sample over that of the field (result significant at only 87 per cent confidence). The X-ray emitting AGN fractions for the BX/MD and LAE samples are found to be 6.9_{-4.4}^{+9.2} and 2.9_{-1.6}^{+2.9} per cent, respectively, for protocluster AGN with L_{2-10 keV}>4.6x10^{43} erg s^{-1} at z=2.30. These findings are similar to results from the z=3.09 protocluster in the SSA 22 field found by Lehmer et al. (2009), in that both suggest AGN activity is favoured in dense environments at z>2.Comment: 8 pages, 2 figures. Accepted for publication in MNRAS

A high-resolution mRNA expression time course of embryonic development in zebrafish.

We have produced an mRNA expression time course of zebrafish development across 18 time points from 1 cell to 5 days post-fertilisation sampling individual and pools of embryos. Using poly(A) pulldown stranded RNA-seq and a 3' end transcript counting method we characterise temporal expression profiles of 23,642 genes. We identify temporal and functional transcript co-variance that associates 5024 unnamed genes with distinct developmental time points. Specifically, a class of over 100 previously uncharacterised zinc finger domain containing genes, located on the long arm of chromosome 4, is expressed in a sharp peak during zygotic genome activation. In addition, the data reveal new genes and transcripts, differential use of exons and previously unidentified 3' ends across development, new primary microRNAs and temporal divergence of gene paralogues generated in the teleost genome duplication. To make this dataset a useful baseline reference, the data can be browsed and downloaded at Expression Atlas and Ensembl

Response to novel objects and foraging tasks by common marmoset (Callithrix Jacchus) female Pairs

Many studies have shown that environmental enrichment can significantly improve the psychological well-being of captive primates, increasing the occurrence of explorative behavior and thus reducing boredom. The response of primates to enrichment devices may be affected by many factors such as species, sex, age, personality and social context. Environmental enrichment is particularly important for social primates living in unnatural social groupings (i.e. same-sex pairs or singly housed animals), who have very few, or no, benefits from the presence of social companions in addition to all the problems related to captivity (e.g. increased inactivity). This study analyses the effects of enrichment devices (i.e. novel objects and foraging tasks) on the behavior of common marmoset (Callithrix jacchus) female pairs, a species that usually lives in family groups. It aims to determine which aspects of an enrichment device are more likely to elicit explorative behaviors, and how aggressive and stress-related behaviors are affected by its presence. Overall, the marmosets explored foraging tasks significantly longer than novel objects. The type of object, which varied in size, shape and aural responsiveness (i.e. they made a noise when the monkey touched them), did not affect the response of the monkeys, but they explored objects that were placed higher in the enclosure more than those placed lower down.Younger monkeys were more attracted to the enrichment devices than the older ones. Finally, stress-related behavior (i.e. scratching) significantly decreased when the monkeys were presented with the objects; aggressive behavior as unaffected. This study supports the importance of environmental enrichment for captive primates and shows that in marmosets its effectiveness strongly depends upon the height of the device in the enclosure and the presence of hidden food. The findings can be explained ifone considers the foraging behavior of wild common marmosets. Broader applications for the research findings are suggested in relation to enrichment

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd