Assessing the Factorial Validity of the Attitudes and Belief Scale 2-Abbreviated Version: A Call for the Development a Gold Standard Method of Measuring Rational and Irrational Beliefs

Rational Emotive Behaviour Therapy (REBT) does not possess a measure of rational and irrational beliefs that meets internationally recognised standards for acceptable psychometric properties. Without such a measure the theory/practice of REBT cannot be rigorously evaluated, thus undermining its scientific veracity. The current study investigates the validity and reliability of a recently developed measure of rational and irrational beliefs: the Attitudes and Belief Scale 2-Abbreviated Version (ABS-2-AV). University students from three countries completed the ABS-2-AV (N = 397). An alternative models framework using confirmatory factor analysis indicated that a theoretically consistent eight-factor model of the ABS-2-AV provided the best fit of the data. A number of post-hoc modifications were required in order to achieve acceptable model fit results, and these modifications revealed important methodological limitations with the ABS-2-AV. Results indicated that the validity of the ABS-2-AV was undermined due to items measuring both the psychological process of interest (rational and irrational beliefs) and the context in which these beliefs processes are presented. This is a serious methodological limitation of the ABS-2 and all questionnaires derived from it, including the ABS-2-AV. This methodological limitation resulted in the ABS-2-AV possessing poor internal reliability. These limitations are discussed in relation to the broader REBT literature and the impact such problems have on research and practice. A call is made for REBT researchers to come together to develop a “gold standard” method of assessing rational and irrational beliefs that meets international standard for psychometric excellence

Prevention of “Humanized” Diabetogenic CD8 T-Cell Responses in HLA-Transgenic NOD Mice by a Multipeptide Coupled-Cell Approach

OBJECTIVE: Type 1 diabetes can be inhibited in standard NOD mice by autoantigen-specific immunotherapy targeting pathogenic CD8+ T-cells. NOD.beta2m(null).HHD mice expressing human HLA-A2.1 but lacking murine major histocompatibility complex class I molecules develop diabetes characterized by CD8 T-cells recognizing certain autoantigenic peptides also targeted in human patients. These include peptides derived from the pancreatic beta-cell proteins insulin (INS1/2 A(2-10) and INS1 B(5-14)) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(265-273) and IGRP(228-236)). Hence, NOD.beta2m(null).HHD mice represent a model system for developing potentially clinically translatable interventions for suppressing diabetogenic HLA-A2.1-restricted T-cell responses. RESEARCH DESIGN AND METHODS: Starting at 4-6 weeks of age, NOD.beta2m(null).HHD female mice were injected intravenously with syngeneic splenocytes to which various admixtures of the four above-mentioned peptides were bound by the cross-linking agent ethylene carbodiimide (ECDI). RESULTS: Treatment with such cells bearing the complete cocktail of INS and IGRP epitopes (designated INS/IGRP-SPs) significantly inhibited diabetes development in NOD.beta2m(null).HHD recipients compared with controls receiving splenocytes coupled with an irrelevant HLA-A2.1-restricted Flu16 peptide. Subsequent analyses found syngeneic splenocytes bearing the combination of the two ECDI-coupled IGRPs but not INS peptides (IGRP-SPs or INS-SPs) effectively inhibited diabetes development in NOD.beta2m(null).HHD mice. This result was supported by enzyme-linked immunospot (ELISPOT) analyses indicating combined INS/IGRP-SPs diminished HLA-A2.1-restricted IGRP but not INS autoreactive CD8+ T-cell responses in NOD.beta2m(null).HHD mice. CONCLUSIONS: These data support the potential of a cell therapy approach targeting HLA-A2.1-restricted IGRP autoreactive CD8 T-cells as a diabetes intervention approach in appropriate human patients

Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity

Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet b cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell–mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice. Methods and Findings: Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8 + T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8 + T cells in the pancreatic islets through controlling dipeptidyl peptidase I activity. Moreover, the gene targeting for cathepsin L with application of in vivo siRNA administration successfully prevented CY-induced diabetes of NOD mice. Finally, cathepsin L mRNA expression of peripheral CD8 + T cells from NOD mice developing spontaneous T1D was significantly increased compared with that from control mice. Conclusions: Our results identified a novel function of cathepsin L as an enzyme whose activity is essential for the progression of CD8 + T cell-mediated autoimmune diabetes, and inhibition of cathepsin L as a powerful therapeutic strateg

Absence of an association of human polyomavirus and papillomavirus infection with lung cancer in China: a nested case–control study

BACKGROUND: Studies of human polyomavirus (HPyV) infection and lung cancer are limited and those regarding the association of human papillomavirus (HPV) infection and lung cancer have produced inconsistent results. METHODS: We conducted a nested case–control study to assess the association between incident lung cancer of various histologies and evidence of prior infection with HPyVs and HPVs. We selected serum from 183 cases and 217 frequency matched controls from the Yunnan Tin Miner’s Cohort study, which was designed to identify biomarkers for early detection of lung cancer. Using multiplex liquid bead microarray (LBMA) antibody assays, we tested for antibodies to the VP1 structural protein and small T antigen (ST-Ag) of Merkel cell, KI, and WU HPyVs. We also tested for antibodies against HPV L1 structural proteins (high-risk types 16, 18, 31, 33, 52, and 58 and low-risk types 6 and 11) and E6 and E7 oncoproteins (high risk types 16 and 18). Measures of antibody reactivity were log transformed and analyzed using logistic regression. RESULTS: We found no association between KIV, WUV, and MCV antibody levels and incident lung cancer (P-corrected for multiple comparisons >0.10 for all trend tests). We also found no association with HPV-16, 18, 31, 33, 52, and 58 seropositivity (P-corrected for multiple comparisons >0.05 for all). CONCLUSIONS: Future studies of infectious etiologies of lung cancer should look beyond HPyVs and HPVs as candidate infectious agents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2381-3) contains supplementary material, which is available to authorized users

Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function

Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation

James M. Buchanan: Neoclassical, Austrian, Neither, or Both?

James McGill Buchanan (1919-2013) received the Nobel Memorial Prize in 1986 for his work in public choice theory, set out in his The Calculus of Consent (1962), co-authored with Gordon Tullock. The Virginia School of Political Economy can be seen as a product of the work of Buchanan and Tullock, along with Ronald Coase, who published his ground-breaking paper on “The Problem of Social Cost” in 1960 while he was at the University of Virginia. This school of thought is generally thought to be in some ill-defined sense allied to the Austrian school of economics, mainly perhaps because of a shared pro-market policy stance. On the other hand, links between Buchanan and neoclassical economists such as Friedman and Stigler are frequently drawn, again probably with the pro-market policy recommendations of each in mind. It is notable that Buchanan, Hayek, and Friedman were all at various times presidents of the Mont Pelerin Society. Yet the differences between neoclassical and Austrian perspectives are profound. It has often been said that the one can be characterized as “equilibrium always” and the other as “equilibrium never”. The case of Buchanan and the Virginia School is therefore extremely interesting for the historian of economic thought. Significant questions are raised about the scope for reconciliation between schools of thought at the most profound levels of methodology and social philosophy. I posit that, allowing for a slight amount of breathing room, James Buchanan’s economic writings are more Austrian than anything else. From his earliest writings to his last publications, Buchanan clearly had an Austrian-leaning approach. Additionally, many of the criticisms he laid out about the economics profession were directed toward the more neoclassical minded among his peers. While the act of criticizing neoclassical economists does not indicate that Buchanan was an Austrian, it does seem to lay to rest any conclusions that he was a neoclassical economist himself

Validação da Échelle Douleur Inconfort Nouveau-Né para a cultura brasileira

RESUMO Objetivo Avaliar a confiabilidade e a validade da versão brasileira da Échelle Douleur Inconfort Nouveau-Né, que mensura a dor prolongada em recém-nascidos. Método Estudo metodológico realizado junto com recém-nascidos. Para a coleta foram utilizadas as versões brasileiras da Échelle Douleur Inconfort Nouveau-Né e da Children’s and Infants’ Postoperative Pain Scale. Para a confiabilidade, foram consideradas a equivalência, mensurada pela concordância entre observadores, e a homogeneidade. Para avaliar a validade, foi considerada a abordagem de construto convergente correlacionando as versões brasileiras da Échelle Douleur Inconfort Nouveau-Né e da Children’s and Infants’ Postoperative Pain Scale. Resultados Compuseram a amostra final 96 recém-nascidos. Na avaliação da confiabilidade, o coeficiente de concordância entre observadores variou entre 0,64 e 0,85 para os itens que compõem o instrumento e 0,96 para o escore total. O alfa de Cronbach foi de 0,82. Na avaliação da validade convergente, o coeficiente de correlação de Spearman entre os valores encontrados para as duas escalas foi de 0,79 (p< 0,0001). Conclusão A versão brasileira da Échelle Douleur Inconfort Nouveau-Né é um instrumento confiável e válido para avaliar a dor prolongada em recém-nascidos