183 research outputs found

    Characterisation and evaluation of the regenerative capacity of Stro-4+ enriched bone marrow mesenchymal stromal cells using bovine extracellular matrix hydrogel and a novel biocompatible melt electro-written medical-grade polycaprolactone scaffold

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    Many skeletal tissue regenerative strategies centre around the multifunctional properties of bone marrow derived stromal cells (BMSC) or mesenchymal stem/stromal cells (MSC)/bone marrow derived skeletal stem cells (SSC). Specific identification of these particular stem cells has been inconclusive. However, enriching these heterogeneous bone marrow cell populations with characterised skeletal progenitor markers has been a contributing factor in successful skeletal bone regeneration and repair strategies. In the current studies we have isolated, characterised and enriched ovine bone marrow mesenchymal stromal cells (oBMSCs) using a specific antibody, Stro-4, examined their multipotential differentiation capacity and, in translational studies combined Stro-4+ oBMSCs with a bovine extracellular matrix (bECM) hydrogel and a biocompatible melt electro-written medical-grade polycaprolactone scaffold, and tested their bone regenerative capacity in a small in vivo, highly vascularised, chick chorioallantoic membrane (CAM) model and a preclinical, critical-sized ovine segmental tibial defect model.Proliferation rates and CFU-F formation were similar between unselected and Stro-4+ oBMSCs. Col1A1, Col2A1, mSOX-9, PPARG gene expression were upregulated in respective osteogenic, chondrogenic and adipogenic culture conditions compared to basal conditions with no significant difference between Stro-4+ and unselected oBMSCs. In contrast, proteoglycan expression, alkaline phosphatase activity and adipogenesis were significantly upregulated in the Stro-4+ cells. Furthermore, with extended cultures, the oBMSCs had a predisposition to maintain a strong chondrogenic phenotype. In the CAM model Stro-4+ oBMSCs/bECM hydrogel was able to induce bone formation at a femur fracture site compared to bECM hydrogel and control blank defect alone. Translational studies in a critical-sized ovine tibial defect showed autograft samples contained significantly more bone, (4250.63 mm3, SD = 1485.57) than blank (1045.29 mm3, SD = 219.68) ECM-hydrogel (1152.58 mm3, SD = 191.95) and Stro-4+/ECM-hydrogel (1127.95 mm3, SD = 166.44) groups.Stro-4+ oBMSCs demonstrated a potential to aid bone repair in vitro and in a small in vivo bone defect model using select scaffolds. However, critically, translation to a large related preclinical model demonstrated the complexities of bringing small scale reported stem-cell material therapies to a clinically relevant model and thus facilitate progression to the clinic

    Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC

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    Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58–0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47–076 and 0.48–0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients

    Ab initio atomistic thermodynamics and statistical mechanics of surface properties and functions

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    Previous and present "academic" research aiming at atomic scale understanding is mainly concerned with the study of individual molecular processes possibly underlying materials science applications. Appealing properties of an individual process are then frequently discussed in terms of their direct importance for the envisioned material function, or reciprocally, the function of materials is somehow believed to be understandable by essentially one prominent elementary process only. What is often overlooked in this approach is that in macroscopic systems of technological relevance typically a large number of distinct atomic scale processes take place. Which of them are decisive for observable system properties and functions is then not only determined by the detailed individual properties of each process alone, but in many, if not most cases also the interplay of all processes, i.e. how they act together, plays a crucial role. For a "predictive materials science modeling with microscopic understanding", a description that treats the statistical interplay of a large number of microscopically well-described elementary processes must therefore be applied. Modern electronic structure theory methods such as DFT have become a standard tool for the accurate description of individual molecular processes. Here, we discuss the present status of emerging methodologies which attempt to achieve a (hopefully seamless) match of DFT with concepts from statistical mechanics or thermodynamics, in order to also address the interplay of the various molecular processes. The new quality of, and the novel insights that can be gained by, such techniques is illustrated by how they allow the description of crystal surfaces in contact with realistic gas-phase environments.Comment: 24 pages including 17 figures, related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

    Low-diffusion Xe-He gas mixtures for rare-event detection: electroluminescence yield

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    High pressure xenon Time Projection Chambers (TPC) based on secondary scintillation (electroluminescence) signal amplification are being proposed for rare event detection such as directional dark matter, double electron capture and double beta decay detection. The discrimination of the rare event through the topological signature of primary ionisation trails is a major asset for this type of TPC when compared to single liquid or double-phase TPCs, limited mainly by the high electron diffusion in pure xenon. Helium admixtures with xenon can be an attractive solution to reduce the electron diffu- sion significantly, improving the discrimination efficiency of these optical TPCs. We have measured the electroluminescence (EL) yield of Xe–He mixtures, in the range of 0 to 30% He and demonstrated the small impact on the EL yield of the addition of helium to pure xenon. For a typical reduced electric field of 2.5 kV/cm/bar in the EL region, the EL yield is lowered by ∼ 2%, 3%, 6% and 10% for 10%, 15%, 20% and 30% of helium concentration, respectively. This decrease is less than what has been obtained from the most recent simulation framework in the literature. The impact of the addition of helium on EL statistical fluctuations is negligible, within the experimental uncertainties. The present results are an important benchmark for the simulation tools to be applied to future optical TPCs based on Xe-He mixtures. [Figure not available: see fulltext.]

    Examining Contextual Factors and Individual Value Dimensions of Healthcare Providers Intention to Adopt Electronic Health Technologies in Developing Countries

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    Part 5: Research in ProgressInternational audienceDespite substantial research on electronic health (e-Health) adoption, there still exist vast differences between resource-rich and resource-poor populations regarding Information Technology adoption. To help bridge the technological gulf between developed and developing countries, this research-in-progress paper examines healthcare providers’ intention to adopt e-health technologies from two perspectives 1) contextual factors (i.e. specific to developing world settings) and 2) individual value dimensions (i.e. cultural, utilitarian, social and personal). The primary output of this paper is a theoretical model merging both the contextual factors and value dimensions; this forms a strong baseline to examine and help ensure the successful adoption of e-Health technologies within developing countries. Future research will be performed to validate the model developed in this paper, with a specific focus on mobile Health in Malawi, Africa

    Boosting background suppression in the NEXT experiment through Richardson-Lucy deconvolution

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    Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of similar to 10(27) yr, requiring suppressing backgrounds to < 1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utmost importance. The NEXT experiment exploits differences in the spatial ionization patterns of double beta decay and single-electron events to discriminate signal from background. While the former display two Bragg peak dense ionization regions at the opposite ends of the track, the latter typically have only one such feature. Thus, comparing the energies at the track extremes provides an additional rejection tool. The unique combination of the topology-based background discrimination and excellent energy resolution (1% FWHM at the Q-value of the decay) is the distinguishing feature of NEXT. Previous studies demonstrated a topological background rejection factor of 5 when reconstructing electron-positron pairs in the Tl-208 1.6 MeV double escape peak (with Compton events as background), recorded in the NEXT-White demonstrator at the Laboratorio Subterraneo de Canfranc, with 72% signal efficiency. This was recently improved through the use of a deep convolutional neural network to yield a background rejection factor of similar to 10 with 65% signal efficiency. Here, we present a new reconstruction method, based on the Richardson-Lucy deconvolution algorithm, which allows reversing the blurring induced by electron diffusion and electroluminescence light production in the NEXT TPC. The new method yields highly refined 3D images of reconstructed events, and, as a result, significantly improves the topological background discrimination. When applied to real-data 1.6 MeV e(-)e(+) pairs, it leads to a background rejection factor of 27 at 57% signal efficiency.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program grants SEV-2014-0398 and CEX2018-000867-S, and the Maria de Maeztu Program MDM-2016-0692; the Generalitat Valenciana under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014 and under projects UID/04559/2020 to fund the activities of LIBPhys-UC; the U.S. Department of Energy under contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); the University of Texas at Arlington (U.S.A.); and the Pazy Foundation (Israel) under grants 877040 and 877041. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. JM-A acknowledges support from Fundacion Bancaria "la Caixa" (ID 100010434), grant code LCF/BQ/PI19/11690012. AS acknowledges support from the Kreitman School of Advanced Graduate Studies at Ben-Gurion University. Documen
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