Material parameter estimation and hypothesis testing on a 1D viscoelastic stenosis model: Methodology

This is the post-print version of the final published paper that is available from the link below. Copyright @ 2013 Walter de Gruyter GmbH.Non-invasive detection, localization and characterization of an arterial stenosis (a blockage or partial blockage in the artery) continues to be an important problem in medicine. Partial blockage stenoses are known to generate disturbances in blood flow which generate shear waves in the chest cavity. We examine a one-dimensional viscoelastic model that incorporates Kelvin–Voigt damping and internal variables, and develop a proof-of-concept methodology using simulated data. We first develop an estimation procedure for the material parameters. We use this procedure to determine confidence intervals for the estimated parameters, which indicates the efficacy of finding parameter estimates in practice. Confidence intervals are computed using asymptotic error theory as well as bootstrapping. We then develop a model comparison test to be used in determining if a particular data set came from a low input amplitude or a high input amplitude; this we anticipate will aid in determining when stenosis is present. These two thrusts together will serve as the methodological basis for our continuing analysis using experimental data currently being collected.National Institute of Allergy and Infectious Diseases, Air Force Office of Scientific Research, Department of Education, and Engineering and Physical Sciences Research Council

High-order space-time finite element schemes for acoustic and viscodynamic wave equations with temporal decoupling

Copyright @ 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.We revisit a method originally introduced by Werder et al. (in Comput. Methods Appl. Mech. Engrg., 190:6685–6708, 2001) for temporally discontinuous Galerkin FEMs applied to a parabolic partial differential equation. In that approach, block systems arise because of the coupling of the spatial systems through inner products of the temporal basis functions. If the spatial finite element space is of dimension D and polynomials of degree r are used in time, the block system has dimension (r + 1)D and is usually regarded as being too large when r > 1. Werder et al. found that the space-time coupling matrices are diagonalizable over inline image for r ⩽100, and this means that the time-coupled computations within a time step can actually be decoupled. By using either continuous Galerkin or spectral element methods in space, we apply this DG-in-time methodology, for the first time, to second-order wave equations including elastodynamics with and without Kelvin–Voigt and Maxwell–Zener viscoelasticity. An example set of numerical results is given to demonstrate the favourable effect on error and computational work of the moderately high-order (up to degree 7) temporal and spatio-temporal approximations, and we also touch on an application of this method to an ambitious problem related to the diagnosis of coronary artery disease

The Cochrane Skin Group: a vanguard for developing and promoting evidence-based dermatology

Aim The Cochrane Skin Group (CSG) is part of the international Cochrane Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and disseminates high quality evidence-based summaries on the prevention, diagnosis and treatment of skin diseases. We present a synopsis of the history, scope and priorities of the CSG. In addition, we report outcomes of CSG reviews and critically assess clinical value. Methods Descriptive analysis of systematic reviews published by the CSG since its inception including output, impact factor, associated methodological studies, and influence in clinical guidelines, promoting patient and public engagement and in triggering new primary research. Results The CSG started in 1997, and has published 61 reviews, 34 protocols and 31 registered titles by August 2013. The CSG scope includes 1000 skin diseases; 80% of reviews cover the top ten diagnoses and 40% of reviews provide clear guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011 which places it alongside top dermatology journals. CSG reviews are typically broad in focus and have been shown to be of better quality than non-Cochrane reviews. They are highly cited in clinical guidelines. Several reviews have identified evidence gaps that have led to better primary research. Conclusions The CSG has emerged as a vanguard of evidence-based dermatology by growing a community interested in applying best external evidence to the care of skin patients and by identifying topics for research. CSG reviews are high impact, clinically relevant and have tangibly influenced international dermatology clinical practice guidelines and new research

The Impact of Fillers on Lineup Performance

Filler siphoning theory posits that the presence of fillers (known innocents) in a lineup protects an innocent suspect from being chosen by siphoning choices away from that innocent suspect. This mechanism has been proposed as an explanation for why simultaneous lineups (viewing all lineup members at once) induces better performance than showups (one-person identification procedures). We implemented filler siphoning in a computational model (WITNESS, Clark, Applied Cognitive Psychology 17:629–654, 2003), and explored the impact of the number of fillers (lineup size) and filler quality on simultaneous and sequential lineups (viewing lineups members in sequence), and compared both to showups. In limited situations, we found that filler siphoning can produce a simultaneous lineup performance advantage, but one that is insufficient in magnitude to explain empirical data. However, the magnitude of the empirical simultaneous lineup advantage can be approximated once criterial variability is added to the model. But this modification works by negatively impacting showups rather than promoting more filler siphoning. In sequential lineups, fillers were found to harm performance. Filler siphoning fails to clarify the relationship between simultaneous lineups and sequential lineups or showups. By incorporating constructs like filler siphoning and criterial variability into a computational model, and trying to approximate empirical data, we can sort through explanations of eyewitness decision-making, a prerequisite for policy recommendations.Charges for publication of this article sponsored by University of Oklahoma Libraries Open Access/Subvention Fund.Ye

Loss of Frrs1l disrupts synaptic AMPA receptor function, and results in neurodevelopmental, motor, cognitive and electrographical abnormalities

Loss of function mutations in the human AMPA receptor-associated protein, ferric chelate reductase 1-like (FRRS1L), are associated with a devastating neurological condition incorporating choreoathetosis, cognitive deficits and epileptic encephalopathies. Furthermore, evidence from overexpression and ex vivo studies have implicated FRRS1L in AMPA receptor biogenesis, suggesting that changes in glutamatergic signalling might underlie the disorder. Here, we investigated the neurological and neurobehavioural correlates of the disorder using a mouse Frrs1l null mutant. The study revealed several neurological defects that mirrored those seen in human patients. We established that mice lacking Frrs1l suffered from a broad spectrum of early-onset motor deficits with no progressive, age-related deterioration. Moreover, Frrs1l -/- mice were hyperactive irrespective of test environment, exhibited working memory deficits and displayed significant sleep fragmentation. Longitudinal electroencephalographic recordings also revealed abnormal EEG in Frrs1l -/- mice. Parallel investigations into disease aetiology identified a specific deficiency in AMPA receptor levels in the brain of Frrs1l -/- mice, while the general levels of several other synaptic components remained unchanged with no obvious alterations in the number of synapses. Furthermore, we established that Frrsl1 deletion results in an increased proportion of immature AMPA receptors, indicated by incomplete glycosylation of GLUA2 and GLUA4 AMPA receptor proteins. This incomplete maturation leads to cytoplasmic retention and a reduction of those specific AMPA receptor levels in the postsynaptic membrane. Overall, this study determines, for the first time in vivo, how loss of FRRS1L function can affect glutamatergic signalling and provides mechanistic insight into the development and progression of a human hyperkinetic disorder

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199

Spatial Analyses of Mono, Di and Trinucleotide Trends in Plant Genes

Genomic DNA sequences display compositional heterogeneity on many scales. In this paper we analyzed tendencies and anomalies in the occurence of mono, di and trinucleotides in structural regions of plant genes. Representation of these trends as a function of position along genic sequences highlighted compositional features peculiar of either monocots or eudicots that were remarkably uniform within these two evolutionary clades. The most evident of these features appeared in the form of gradient of base content along the direction of transcription. The robustness of such a representation was validated in sequences sub-datasets generated considering structural and compositional features such as total length of cds, overall GC content and genic orientation in the genome. Piecewise regression analyses indicated that the gradients could be conveniently approximated to a two segmented model where a first region featuring a steep slope is followed by a second segment fitting a milder variation. In general, monocots species showed steeper segments than eudicots. The guanine gradient was the most distinctive feature between the two evolutionary clades, being moderately increasing in eudicots and firmly decreasing in monocots. Single gene investigation revealed that a high proportion of genes show compositional trends compatible with a segmented model suggesting that these features are essential attributes of gene organization. Dinucleotide and trinucleotide biases were referred to expectation based on a random union of the component elements. The average bias at dinucleotide level identified a significant undererpresentation of some dinucleotide and the overrepresention of others. The bias at trinucleotide level was on average low. Finally, the analysis of bryophyte coding sequences showed mononucleotide, dinucleotide and trinucleotide compositional trends resembling those of higher plants. This finding suggested that the emergenge of compositional bias is an ancient event in evolution which was already present at the time of land conquest by green plants

Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany

Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case–control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25–0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to <30 kg m−2 (2.76, 1.07–7.12) and obese women (3.30, 1.25–8.72), when compared with women with BMI <23 kg m−2 (P for trend <0.01). BMI was not associated with risk of CRC among HRT users (P for interaction <0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study