3D Printable Vascular Networks Generated by Accelerated Constrained Constructive Optimization for Tissue Engineering.

One of the greatest challenges in fabricating artificial tissues and organs is the incorporation of vascular networks to support the biological requirements of the embedded cells, encouraging tissue formation and maturation. With the advent of 3D printing technology, significant progress has been made with respect to generating vascularized artificial tissues. Current algorithms to generate arterial/venous trees are computationally expensive and offer limited freedom to optimize the resulting structures. Furthermore, there is no method for algorithmic generation of vascular networks that can recapitulate the complexity of the native vasculature for more than two trees, and export directly to a 3D printing format. Here, we report such a method, using an accelerated constructive constrained optimization approach, by decomposing the process into construction, optimization, and collision resolution stages. The new approach reduces computation time to minutes at problem sizes where previous implementations have reported days. With the optimality criterion of maximizing the volume of useful tissue which could be grown around such a network, an approach of alternating stages of construction and batch optimization of all node positions is introduced and shown to yield consistently more optimal networks. The approach does not place a limit on the number of interpenetrating networks that can be constructed in a given space; indeed we demonstrate a biomimetic, liver-like tissue model. Methods to account for the limitations of 3D printing are provided, notably the minimum feature size and infill at sharp angles, through padding and angle reduction, respectively.EPSRC Doctoral Training Partner-ship Award (EP/N509620/1) EPSRC (EP/R511675/1 & EP/N509620/1) Isaac Newton Trust Rosetrees Trust (M787). Cambridge Trust CONACyT (Mexico) EPSRC Cambridge & Cranfield Doctoral Training Centre in Ultra Precision (EP/K503241/1

Physical and biological characterization of ferromagnetic fiber networks: effect of fibrin deposition on short-term in vitro responses of human osteoblasts.

Ferromagnetic fiber networks have the potential to deform in vivo imparting therapeutic levels of strain on in-growing periprosthetic bone tissue. 444 Ferritic stainless steel provides a suitable material for this application due to its ability to support cultures of human osteoblasts (HObs) without eliciting undue inflammatory responses from monocytes in vitro. In the present article, a 444 fiber network, containing 17 vol% fibers, has been investigated. The network architecture was obtained by applying a skeletonization algorithm to three-dimensional tomographic reconstructions of the fiber networks. Elastic properties were measured using low-frequency vibration testing, providing globally averaged properties as opposed to mechanical methods that yield only local properties. The optimal region for transduction of strain to cells lies between the ferromagnetic fibers. However, cell attachment, at early time points, occurs primarily on fiber surfaces. Deposition of fibrin, a fibrous protein involved in acute inflammatory responses, can facilitate cell attachment within this optimal region at early time points. The current work compared physiological (3 and 5 g·L(-1)) and supraphysiological fibrinogen concentrations (10 g·L(-1)), using static in vitro seeding of HObs, to determine the effect of fibrin deposition on cell responses during the first week of cell culture. Early cell attachment within the interfiber spaces was observed in all fibrin-containing samples, supported by fibrin nanofibers. Fibrin deposition influenced the seeding, metabolic activity, and early stage differentiation of HObs cultured in the fibrin-containing fiber networks in a concentration-dependant manner. While initial cell attachment for networks with fibrin deposited from low physiological concentrations was similar to control samples without fibrin deposition, significantly higher HObs attached onto high physiological and supraphysiological concentrations. Despite higher cell numbers with supraphysiological concentrations, cell metabolic activities were similar for all fibrinogen concentrations. Further, cells cultured on supraphysiological concentrations exhibited lower cell differentiation as measured by alkaline phosphatase activity at early time points. Overall, the current study suggests that physiological fibrinogen concentrations would be more suitable than supraphysiological concentrations for supporting early cell activity in porous implant coatings.This is the author accepted manuscript. The final version is available from Mary Ann Liebert at http://online.liebertpub.com/doi/abs/10.1089/ten.TEA.2014.0211?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

Translating and validating a Training Needs Assessment tool into Greek

<p>Abstract</p> <p>Background</p> <p>The translation and cultural adaptation of widely accepted, psychometrically tested tools is regarded as an essential component of effective human resource management in the primary care arena. The Training Needs Assessment (TNA) is a widely used, valid instrument, designed to measure professional development needs of health care professionals, especially in primary health care. This study aims to describe the translation, adaptation and validation of the TNA questionnaire into Greek language and discuss possibilities of its use in primary care settings.</p> <p>Methods</p> <p>A modified version of the English self-administered questionnaire consisting of 30 items was used. Internationally recommended methodology, mandating forward translation, backward translation, reconciliation and pretesting steps, was followed. Tool validation included assessing item internal consistency, using the alpha coefficient of Cronbach. Reproducibility (test – retest reliability) was measured by the kappa correlation coefficient. Criterion validity was calculated for selected parts of the questionnaire by correlating respondents' research experience with relevant research item scores. An exploratory factor analysis highlighted how the items group together, using a Varimax (oblique) rotation and subsequent Cronbach's alpha assessment.</p> <p>Results</p> <p>The psychometric properties of the Greek version of the TNA questionnaire for nursing staff employed in primary care were good. Internal consistency of the instrument was very good, Cronbach's alpha was found to be 0.985 (p < 0.001) and Kappa coefficient for reproducibility was found to be 0.928 (p < 0.0001). Significant positive correlations were found between respondents' current performance levels on each of the research items and amount of research involvement, indicating good criterion validity in the areas tested. Factor analysis revealed seven factors with eigenvalues of > 1.0, KMO (Kaiser-Meyer-Olkin) measure of sampling adequacy = 0.680 and Bartlett's test of sphericity, p < 0.001.</p> <p>Conclusion</p> <p>The translated and adapted Greek version is comparable with the original English instrument in terms of validity and reliability and it is suitable to assess professional development needs of nursing staff in Greek primary care settings.</p

Processes and coastal dynamics in the Ensenada de Marbella: recent morphosedimentary evolution

La Ensenada de Marbella ha experimentado en las últimas décadas cambios físicos y socio-económicos sustanciales debidos fundamentalmente a una transformación en el modelo económico y un desarrollo acusado del turismo residencial y todos los impactos en los usos del suelo relacionado con ello. Sin embargo, las causas de la alteración de la dinámica litoral también hay que buscarlas en cambios en la morfología del nearshore y en la dinámica sedimentaria. Para analizar la morfodinámica de la ensenada en varios escenarios temporales, simulaciones de oleaje sobre batimetrías del 1888 y actuales revelan cambios importantes en los patrones dispersión de la energía y el funcionamiento de la bahía a través de complejas células litorales de transporte. El análisis de los procesos dinámicos en la zona del nearshore y el estudio volumétrico a través de modelos de batimetrías secuenciales muestran como dichos cambios morfológicos de los fondos costeros pueden o no estar relacionados con cambios a largo plazo en la línea de costa, y por tanto ser co-responsables de los procesos de erosión y acreción acelerados evidentes a lo largo de la Ensenada

Biomimetic and electroactive 3D scaffolds for human neural crest-derived stem cell expansion and osteogenic differentiation

AbstractOsteoporosis is a skeletal disease characterized by bone loss and bone microarchitectural deterioration. The combination of smart materials and stem cells represents a new therapeutic approach. In the present study, highly porous scaffolds are prepared by combining the conducting polymer PEDOT:PSS with collagen type I, the most abundant protein in bone. The inclusion of collagen proves to be an effective way to modulate their mechanical properties and it induces an increase in scaffolds’ electrochemical impedance. The biomimetic scaffolds support neural crest-derived stem cell osteogenic differentiation, with no need for scaffold pre-conditioning contrarily to other reports.</jats:p

Public Opinion on Migration and the Role of the Media in the Context of the “European Refugee Crisis”

This book presents an overview of European migration policy and the various institutional arrangements within and between various actors, such as local councils, local media, local economies, and local civil society initiatives. Both the role of local authorities in this policy field and their cooperation with civil society initiatives or networks are under-explored topics for research. In response, this book provides a range of detailed case studies focusing on the six main groups of national and administrative traditions in Europe: Germanic, Scandinavian, Napoleonic, Southeastern European, Central-Eastern European and Anglo-Saxon.Peer reviewe

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

Background: A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). Results: We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an `autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. Conclusions: 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi