482 research outputs found

    Development and validation of a self-report measure of epistemic trust

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    Epistemic trust (ET) refers to trust in communicated knowledge. This paper describes the development and validation of a new self-report questionnaire, the Epistemic Trust, Mistrust and Credulity Questionnaire (ETMCQ). We report on two studies (Study 1, n = 500; Study 2, n = 705) examining the psychometric properties of the ETMCQ and the relationship between EMTCQ scores (i.e., an individual’s epistemic stance) and exposure to adverse childhood experiences, mental health symptoms, attachment, mentalizing and general self-efficacy. The factor structure of the ETMCQ was examined using Exploratory and Confirmatory Factor Analyses, and its reliability and test-retest reliability were tested. Both studies yielded three correlated yet distinct factors – Trust, Mistrust and Credulity – and confirmed the reliability and validity of the ETMCQ. Preregistered hypotheses were confirmed and replicated across both studies. Main findings suggest intriguing links between the ETMCQ and developmental psychopathology constructs and are consistent with thinking on the role of epistemic stance in undermining adaptation and increasing the developmental risk of mental health problems. Mistrust and Credulity scores were associated with childhood adversity and higher scores on the global psychopathology severity index and both factors partially mediated the link between early adversity and mental health symptoms. Mistrust and Credulity were positively associated with difficulties in understanding mental states and insecure attachment styles. Post-hoc analysis identified that different attachment styles were associated with differences in epistemic stance. In addition, Trust was not associated with reduced levels of mental health symptoms and did not moderate the impact of childhood adversity – findings are congruent with the suggestion that the reduction of mistrust and credulity may be crucial common factors in promoting resilience and the effectiveness of psychotherapeutic interventions. This investigation and the ETMCQ provide an empirical measure of what until now has been largely a theoretical concept and open new avenues for future research

    Development of a general calibration model and long-term performance evaluation of low-cost sensors for air pollutant gas monitoring

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    Assessing the intracity spatial distribution and temporal variability in air quality can be facilitated by a dense network of monitoring stations. However, the cost of implementing such a network can be prohibitive if traditional high-quality, expensive monitoring systems are used. To this end, the Real-time Affordable Multi-Pollutant (RAMP) monitor has been developed, which can measure up to five gases including the criteria pollutant gases carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3), along with temperature and relative humidity. This study compares various algorithms to calibrate the RAMP measurements including linear and quadratic regression, clustering, neural networks, Gaussian processes, and hybrid random forest–linear regression models. Using data collected by almost 70 RAMP monitors over periods ranging up to 18 months, we recommend the use of limited quadratic regression calibration models for CO, neural network models for NO, and hybrid models for NO2 and O3 for any low-cost monitor using electrochemical sensors similar to those of the RAMP. Furthermore, generalized calibration models may be used instead of individual models with only a small reduction in overall performance. Generalized models also transfer better when the RAMP is deployed to other locations. For long-term deployments, it is recommended that model performance be re-evaluated and new models developed periodically, due to the noticeable change in performance over periods of a year or more. This makes generalized calibration models even more useful since only a subset of deployed monitors are needed to build these new models. These results will help guide future efforts in the calibration and use of low-cost sensor systems worldwide.</p

    A Comprehensive Case Study of Macrosegregation in a Steel Ingot

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    This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11663-015-0386-yA case study is presented that examines the macrosegregation and grain structure present in a 12-tonne steel ingot, which was cast for experimental purposes. Details of the casting procedure were well documented and the resulting ingot was characterized using a number of techniques that measured chemical segregation, shrinkage, and porosity. The formation of the porosity and segregation patterns is discussed in reference to the particular grain structure observed in the ingot. It is hoped that this case study can be used as a tool for the validation of future macromodels.This work was undertaken as part of a Project sponsored by Rolls-Royce Power Nuclear plc in collaboration with Sheffield Forgemasters International

    The study of expanded tri-lobed flap in a rabbit model: possible flap model in ear reconstruction?

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    BACKGROUND: Local flaps are widely used in reconstructive surgery. Tri-lobed skin flap is a relatively new flap and there has been no experimental model of this flap. This flap can be used for repair of full thickness defects in the face, ears and alar region. Based on the size of ears in a rabbit, we designed a model of ear reconstruction using expanded tri-lobed flap. Local flaps are more advantageous in that they provide excellent color and texture matching up with those of the face, adequately restore ear contour, place scars in a favorable location and ideally accomplish these goals in a single stage with minimal donor site morbidity. METHODS: Eight adult New Zealand rabbits were divided into two groups. 50 ml round tissue expander were implanted to four rabbits. After completion of the expansion, a superiorly based tri-lobed flap was elevated and a new ear was created from the superior dorsal skin of each rabbit. Scintigraphy with Technetium-99m pertecnetate was performed to evaluate flap viability. RESULTS: Subtotal flap necrosis was seen in all animals in non-expanded group. New ear in dimensions of the original ear was created in expanded group without complication. Perfusion and viability of the flaps were proved by Technetium-99m pertecnetate scintigraphy. CONCLUSION: According to our knowledge this study is the first to demonstrate animal model in tri-lobed flap. Also, our technique is the first application of the trilobed flap to the possible ear reconstruction. We speculated that this flap may be used mastoid based without hair, in human. Also, tri-lobed flap may be an alternative in reconstruction of cylindrical organs such as penis or finger

    The Classic: Bone Morphogenetic Protein

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    This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is © 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res. 1971;50:1392–1406

    MicroRNAs in pulmonary arterial remodeling

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    Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

    Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

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    Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites

    A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction

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    MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl(D139V), that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of Mlkl(D139V) homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO). Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region

    Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkin's Lymphomas

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    Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs
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