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

Towards gene therapy for EBV-associated posttransplant lymphoma with genetically modified EBV-specific cytotoxic T cells

Epstein-Barr virus (EBV)-associated posttransplant lymphoma (PTLD) is a major cause of morbidity/mortality after hematopoietic stem cell (SCT) or solid organ (SOT) transplant. Adoptive immunotherapy with EBV-specific cytotoxic lymphocytes (CTLs), although effective in SCT, is less successful after SOT where lifelong immunosuppression therapy is necessary. We have genetically engineered EBV-CTLs to render them resistant to calcineurin (CN) inhibitor FK506 through retroviral transfer of a calcineurin A mutant (CNA12). Here we examined whether or not FK506-resistant EBV-CTLs control EBV-driven tumor progression in the presence of immunosuppression in a xenogeneic mouse model. NOD/SCID/IL2rγnull mice bearing human B-cell lymphoma were injected with autologous CTLs transduced with either CNA12 or eGFP in the presence/absence of FK506. Adoptive transfer of autologous CNA12-CTLs induced dramatic lymphoma regression despite the presence of FK506, whereas eGFP-CTLs did not. CNA12-CTLs persisted longer, homed to the tumor, and expanded more than eGFP-CTLs in mice treated with FK506. Mice receiving CNA12-CTLs and treated with FK506 survived significantly longer than control-treated animals. Our results demonstrate that CNA12-CTL induce regression of EBV-associated tumors in vivo despite ongoing immunosuppression. Clinical application of this novel approach may enhance the efficacy of adoptive transfer of EBV-CTL in SOT patients developing PTLD without the need for reduction in immunosuppressive therapy

Family structure and posttraumatic stress reactions: a longitudinal study using multilevel analyses

<p>Abstract</p> <p>Background</p> <p>There is limited research on the relevance of family structures to the development and maintenance of posttraumatic stress following disasters. We longitudinally studied the effects of marital and parental statuses on posttraumatic stress reactions after the 2004 Southeast Asian tsunami and whether persons in the same households had more shared stress reactions than others.</p> <p>Method</p> <p>The study included a tourist population of 641 Norwegian adult citizens, many of them from families with children. We measured posttraumatic stress symptoms with the Impact of Event Scale-Revised at 6 months and 2 years post-disaster. Analyses included multilevel methods with mixed effects models.</p> <p>Results</p> <p>Results showed that neither marital nor parental status was significantly related to posttraumatic stress. At both assessments, adults living in the same household reported levels of posttraumatic stress that were more similar to one another than adults who were not living together. Between households, disaster experiences were closely related to the variance in posttraumatic stress symptom levels at both assessments. Within households, however, disaster experiences were less related to the variance in symptom level at 2 years than at 6 months.</p> <p>Conclusions</p> <p>These results indicate that adult household members may influence one another's posttraumatic stress reactions as well as their interpretations of the disaster experiences over time. Our findings suggest that multilevel methods may provide important information about family processes after disasters.</p

Global Analysis of Proline-Rich Tandem Repeat Proteins Reveals Broad Phylogenetic Diversity in Plant Secretomes

Cell walls, constructed by precisely choreographed changes in the plant secretome, play critical roles in plant cell physiology and development. Along with structural polysaccharides, secreted proline-rich Tandem Repeat Proteins (TRPs) are important for cell wall function, yet the evolutionary diversity of these structural TRPs remains virtually unexplored. Using a systems-level computational approach to analyze taxonomically diverse plant sequence data, we identified 31 distinct Pro-rich TRP classes targeted for secretion. This analysis expands upon the known phylogenetic diversity of extensins, the most widely studied class of wall structural proteins, and demonstrates that extensins evolved before plant vascularization. Our results also show that most Pro-rich TRP classes have unexpectedly restricted evolutionary distributions, revealing considerable differences in plant secretome signatures that define unexplored diversity

Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

<p>Abstract</p> <p>Background</p> <p>One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder.</p> <p>Methods and design</p> <p>We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD.</p> <p>The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach.</p> <p>Discussion</p> <p>Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.</p

Science Priorities for Seamounts: Research Links to Conservation and Management

Seamounts shape the topography of all ocean basins and can be hotspots of biological activity in the deep sea. The Census of Marine Life on Seamounts (CenSeam) was a field program that examined seamounts as part of the global Census of Marine Life (CoML) initiative from 2005 to 2010. CenSeam progressed seamount science by collating historical data, collecting new data, undertaking regional and global analyses of seamount biodiversity, mapping species and habitat distributions, challenging established paradigms of seamount ecology, developing new hypotheses, and documenting the impacts of human activities on seamounts. However, because of the large number of seamounts globally, much about the structure, function and connectivity of seamount ecosystems remains unexplored and unknown. Continual, and potentially increasing, threats to seamount resources from fishing and seabed mining are creating a pressing demand for research to inform conservation and management strategies. To meet this need, intensive science effort in the following areas will be needed: 1) Improved physical and biological data; of particular importance is information on seamount location, physical characteristics (e.g. habitat heterogeneity and complexity), more complete and intensive biodiversity inventories, and increased understanding of seamount connectivity and faunal dispersal; 2) New human impact data; these shall encompass better studies on the effects of human activities on seamount ecosystems, as well as monitoring long-term changes in seamount assemblages following impacts (e.g. recovery); 3) Global data repositories; there is a pressing need for more comprehensive fisheries catch and effort data, especially on the high seas, and compilation or maintenance of geological and biodiversity databases that underpin regional and global analyses; 4) Application of support tools in a data-poor environment; conservation and management will have to increasingly rely on predictive modelling techniques, critical evaluation of environmental surrogates as faunal “proxies”, and ecological risk assessment

Design, development and construction of a new medical wrist rehabilitation device: A project review

This paper reviews in detail the design and development procedures for the construction of medical device for the rehabilitation of the wrist. The construction of the actual prototype was carried out with off-the-shelf components. The objective was to develop a functional and low cost device. The system is divided in two main components, one for the rehabilitation of the wrist and the other one to perform proprioception exercises, providing relaxation of the patient’s pain due to injuries on the wrist. All the hardware is assembled in one portable support, capable to make vertical and horizontal adjustments. Both systems are fully controlled through a software specially developed to be used by physiotherapists and patients, allowing also the registration of the rehabilitation evolution.The authors gratefully acknowledge the support given by the staff of the Department of Occupational Therapy of the Hospital of Braga (Portugal) during the development of the prototype